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Trial record 1 of 1 for:    B1931022
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A Study Of Inotuzumab Ozogamicin Versus Investigator's Choice Of Chemotherapy In Patients With Relapsed Or Refractory Acute Lymphoblastic Leukemia

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ClinicalTrials.gov Identifier: NCT01564784
Recruitment Status : Completed
First Posted : March 28, 2012
Results First Posted : January 17, 2018
Last Update Posted : January 17, 2018
Sponsor:
Collaborator:
UCB Pharma
Information provided by (Responsible Party):
Pfizer

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Acute Lymphoblastic Leukemia
Interventions Drug: inotuzumab ozogamicin
Drug: FLAG (fludarabine, cytarabine and G-CSF)
Drug: HIDAC (high dose cytarabine)
Drug: cytarabine and mitoxantrone
Enrollment 327
Recruitment Details  
Pre-assignment Details 164 participants were randomized to Inotuzumab Ozogamicin and 162 to Defined Investigator’s Choice of Chemotherapy. Although only 143 participants were treated in the Defined Investigator’s Choice of Chemotherapy arm, all 162 randomized participants were included in the intention-to-treat (ITT) population.
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status). Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Period Title: Overall Study
Started 164 [1] 143 [2]
Completed 30 10
Not Completed 134 133
Reason Not Completed
Other             1             0
Subject refused further follow-up             1             6
Lost to Follow-up             1             1
Death             131             126
[1]
Treated (164 randomized)
[2]
Treated (162 randomized)
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy Total
Hide Arm/Group Description Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status). Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice. Total of all reporting groups
Overall Number of Baseline Participants 164 143 307
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 164 participants 143 participants 307 participants
45.9  (17.07) 45.6  (16.32) 45.7  (16.70)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 164 participants 143 participants 307 participants
Female
73
  44.5%
51
  35.7%
124
  40.4%
Male
91
  55.5%
92
  64.3%
183
  59.6%
1.Primary Outcome
Title Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed by the Endpoint Adjudication Committee (EAC)
Hide Description CR was the disappearance of leukemia indicated by less than (<) 5 percent (%) marrow blasts & absence of peripheral blood leukemic blasts, with recovery of hematopoiesis defined by absolute neutrophil count (ANC) greater than or equal to (≥)1000 per microliter (/μL) & platelets ≥100,000/μL. C1 extramedullary disease status (i.e. complete disappearance of measurable & non-measurable extramedullary disease with the following exceptions: for participants with at least 1 measurable lesion, all nodal masses greater than (>) 1.5 centimeters (cm) in greatest transverse diameter (GTD) at baseline must have regressed to less than or equal to (≤) 1.5 cm in GTD; all nodal masses ≥1 cm & ≤1.5 cm in GTD at baseline must have regressed to <1 cm GTD or reduced by 75% in sum of products of greatest diameters, no new lesions, spleen & other previously enlarged organs must have regressed in size & must not be palpable) was required. CRi was defined as CR except ANC <1000/μL &/or platelets <100,000/μL.
Time Frame Screening, Day 16 to 28 of Cycles 1, 2 and 3, then every 1 to 2 cycles (or as clinically indicated) up to approximately 4 weeks (end of treatment [EoT]) from the last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT218 population - included the ITT population (all participants randomized) for the initial 218 participants.
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 109 109
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
80.7
(72.1 to 87.7)
29.4
(21.0 to 38.8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method 1-sided p-value based on Chi-square test
Comments If any cell count was <5, p-value was based on Fisher's exact test
Method of Estimation Estimation Parameter Rate difference
Estimated Value 51.4
Confidence Interval (2-Sided) 97.5%
38.4 to 64.3
Estimation Comments [Not Specified]
2.Primary Outcome
Title Overall Survival (OS)
Hide Description OS was defined as the time from randomization to date of death due to any cause. Participants last known to be alive were censored at date of last contact.
Time Frame Up to 5 years after randomization or 2 years from randomization of the last participant, whichever occurs first.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population - included all participants randomized. Although only 143 participants were treated in the Defined Investigator’s Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population.
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 164 162
Median (95% Confidence Interval)
Unit of Measure: Months
7.7
(6.0 to 9.2)
6.2
(4.7 to 8.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0105
Comments [Not Specified]
Method 1-sided stratified log-rank p-value
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.751
Confidence Interval (2-Sided) 97.5%
0.568 to 0.993
Estimation Comments Stratified HR, i.e., based on analysis stratified by randomization stratification factors.
3.Secondary Outcome
Title Duration of Remission (DoR) for Participants Who Achieved CR/CRi (Per Investigator Assessment)
Hide Description DoR was defined as time from date of first response in responders (CR/CRi per Investigator assessment) to date of PFS event (i.e. death, progressive disease [objective progression, relapse from CR/CRi or treatment discontinuation due to global deterioration of health status] or starting new induction therapy or post-therapy stem cell transplant [SCT] without achieving CR/CRi). Responders without PFS events were censored at the last valid disease assessment including follow-up.
Time Frame Up to 2 years from randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT218 population who achieved CR/CRi
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 85 32
Median (95% Confidence Interval)
Unit of Measure: Months
5.4
(4.3 to 8.0)
3.5
(2.2 to 6.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0021
Comments [Not Specified]
Method 1-sided stratified log-rank p-value
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.490
Confidence Interval (2-Sided) 95%
0.297 to 0.809
Estimation Comments Stratified HR, i.e., based on analysis stratified by randomization stratification factors.
4.Secondary Outcome
Title Progression-Free Survival (PFS)
Hide Description PFS was defined as time from date of randomization to earliest date of the following events: death, progressive disease (objective progression, relapse from CR/CRi or treatment discontinuation due to global deterioration of health status) and starting new induction therapy or post-therapy SCT without achieving CR/CRi. Participants without a PFS event at time of analysis were censored at the last valid disease assessment. In addition, participants with documentation of an event after an unacceptably long interval (>28 weeks if there was post-baseline disease assessment, or >12 weeks if there was no post-baseline assessment) since the previous disease assessment were censored at the time of the previous assessment (date of randomization if no post-baseline assessment). Post-study treatment follow-up disease assessments was included. Kaplan–Meier method used and 2-sided 95% confidence interval (CI) calculated based on the Brookmeyer and Crowley method.
Time Frame Up to 2 years from randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Although only 143 participants were treated in the Defined Investigator’s Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population.
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 164 162
Median (95% Confidence Interval)
Unit of Measure: Months
5.0
(3.9 to 5.8)
1.7
(1.4 to 2.1)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method 1-sided stratified log-rank p-value
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.450
Confidence Interval (2-Sided) 97.5%
0.336 to 0.602
Estimation Comments Stratified HR, i.e., based on analysis stratified by randomization stratification factors.
5.Secondary Outcome
Title Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT)
Hide Description HSCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin or Investigator's choice of chemotherapy.
Time Frame Up to 19 weeks from last dose
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Although only 143 participants were treated in the Defined Investigator’s Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population.
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 164 162
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
42.7
(35.0 to 50.6)
11.1
(6.7 to 17.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method 1-sided p-value based on Chi-square test
Comments If any cell count was <5, p-value was based on Fisher's exact test
Method of Estimation Estimation Parameter Rate difference
Estimated Value 31.6
Confidence Interval (2-Sided) 95%
22.6 to 40.6
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi (Per EAC Assessment)
Hide Description MRD analysis was performed at least once in participants with prior assessment of CR or CRi. Bone marrow aspirates, collected at screening and during the study, were sent to the central laboratory and analyzed using multiparametric flow cytometry. The antibody combinations were designed to maximize discrimination between normal and abnormal cells of B-cell lineage and similar maturational stage and included antibodies detecting cluster of differentiation (CD) 9, CD10, CD13, CD19, CD20, CD33, CD34, CD38, CD45, CD58, CD66c, and CD123. A peripheral blood sample was provided if a participant had an inadequate bone marrow aspirate at screening. MRD negativity was considered to have been achieved if the lowest value of MRD from the first date of CR/CRi to EoT was <1 × 10^-4 blasts/nucleated cells.
Time Frame Up to approximately 4 weeks (EoT) from last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT218 population achieving CR/CRi (per EAC Assessment)
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 88 32
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
78.4
(68.4 to 86.5)
28.1
(13.7 to 46.7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method 1-sided p-value based on Chi-Square test
Comments If any cell count is <5, p-value was based on Fisher's exact test
7.Secondary Outcome
Title Cytogenetic Status (Based on Local Laboratory Analysis) of Participants With CR/CRi (Per EAC Assessment)
Hide Description Karyotyping was required locally, at screening and at least once during the study in participants who had abnormal cytogenetics at baseline and who achieved CR/CRi. Data presented below are for participants who achieved CR/CRi per EAC and had abnormal karyotype at screening.
Time Frame Up to approximately 4 weeks (EoT) from last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the ITT218 population who had abnormal cytogenetics at baseline and who achieved CR/CRi
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 54 22
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
3.7
(0.5 to 12.7)
18.2
(5.2 to 40.3)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Abnormal at Screening
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3168
Comments [Not Specified]
Method 1-sided p-value based on Chi-Square test
Comments If any cell count is <5, p-value was based on Fisher's exact test
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Abnormal after remission
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2160
Comments [Not Specified]
Method 1-sided p-value based on Chi-Square test
Comments If any cell count is <5, p-value was based on Fisher's exact test
8.Secondary Outcome
Title Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) and Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing
Hide Description Blood samples were collected and analyzed for inotuzumab ozogamicin serum concentrations using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC/MS/MS) method with a lower limit of quantification of 1.0 nanograms per milliliter (ng/mL). Cmax was the maximum observed concentration occurring between 0-8 hours post-dose. Ctrough was the concentration prior to subsequent dose (pre-dose) occurring after 8 hours. n = number of observations (non-missing concentrations).
Time Frame Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic (PK) evaluable population - included all participants with available PK data.
Arm/Group Title Inotuzumab Ozogamicin
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Overall Number of Participants Analyzed 163
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cmax (Cycle 1 Day 1, 1 hour post-dose) (n=128) 211  (232)
Ctrough (Cycle 4 Day 1, pre-dose) (n=46) 57.9  (29.8)
Cmax (Cycle 4 Day 1, 1 hour post-dose) (n=37) 308  (362)
9.Secondary Outcome
Title Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) Score
Hide Description This questionnaire comprised 30 questions within which are 9 multi-item scales & 6 single-item measures. There are 5 functional scales; physical, role, cognitive, emotional & social, 3 symptom scales; fatigue, pain, & nausea & vomiting, & a global health status/quality of life (QoL) scale. There are 5 single item measures assessing additional symptoms commonly reported by cancer patients (loss of appetite, insomnia, constipation, diarrhea, & dyspnea) & a single item concerning perceived financial impact of the disease. Most questions used a 4 point scale (1='not at all' to 4='very much'); 2 questions used a 7-point scale (1='very poor' to 7='excellent'). Scores were averaged & transformed to a scale ranging from 0 to 100; a higher score indicates a better level of functioning or greater degree of symptoms.
Time Frame Day 1 of each cycle prior to dosing and EoT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Although only 143 participants were treated in the Defined Investigator’s Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 164 162
Mean (Standard Error)
Unit of Measure: Score on a scale
Physical Functioning C2D1 0.48  (1.53) 0.32  (3.55)
Physical Functioning C3D1 3.15  (1.97) -13.33  (7.70)
Physical Functioning C4D1 5.33  (2.84) 0.00 [1]   (NA)
Physical Functioning C5D1 11.52  (3.51) NA [2]   (NA)
Physical Functioning C6D1 7.22  (5.94) NA [2]   (NA)
Physical Functioning EoT -3.38  (2.03) -8.17  (2.67)
Role Functioning C2D1 5.45  (2.79) -1.59  (8.21)
Role Functioning C3D1 11.81  (3.19) -11.11  (5.56)
Role Functioning C4D1 16.67  (5.47) 0.00 [1]   (NA)
Role Functioning C5D1 12.88  (6.10) NA [2]   (NA)
Role Functioning C6D1 16.67  (11.42) NA [2]   (NA)
Role Functioning EoT 1.32  (3.59) -12.37  (4.09)
Emotional Functioning C2D1 5.21  (1.76) 4.76  (6.77)
Emotional Functioning C3D1 7.41  (1.85) -19.44  (10.02)
Emotional Functioning C4D1 5.69  (1.63) 0.00 [1]   (NA)
Emotional Functioning C5D1 6.82  (2.83) NA [2]   (NA)
Emotional Functioning C6D1 2.78  (4.27) NA [2]   (NA)
Emotional Functioning EoT -0.91  (1.80) 4.35  (2.96)
Cognitive Functioning C2D1 4.05  (1.47) 0.00  (3.98)
Cognitive Functioning C3D1 5.79  (2.11) -5.56  (14.70)
Cognitive Functioning C4D1 4.58  (2.86) 16.67 [1]   (NA)
Cognitive Functioning C5D1 0.76  (4.17) NA [2]   (NA)
Cognitive Functioning C6D1 -8.33  (2.51) NA [2]   (NA)
Cognitive Functioning EoT 0.83  (1.82) 0.54  (2.89)
Social Functioning C2D1 4.20  (2.46) -2.38  (7.21)
Social Functioning C3D1 5.56  (3.25) -27.78  (20.03)
Social Functioning C4D1 10.42  (4.95) 0.00 [1]   (NA)
Social Functioning C5D1 12.88  (6.00) NA [2]   (NA)
Social Functioning C6D1 16.67  (5.03) NA [2]   (NA)
Social Functioning EoT 1.82  (2.84) -2.15  (4.78)
Global Health Status C2D1 3.98  (2.03) 0.40  (4.62)
Global Health Status C3D1 9.38  (3.15) -16.67  (12.73)
Global Health Status C4D1 11.25  (3.69) 8.33 [1]   (NA)
Global Health Status C5D1 8.71  (6.68) NA [2]   (NA)
Global Health Status C6D1 0.69  (6.76) NA [2]   (NA)
Global Health Status EoT 0.00  (2.83) -0.40  (3.28)
Dyspnoea C2D1 -5.41  (2.72) -7.94  (6.47)
Dyspnoea C3D1 -7.41  (3.24) 11.11  (11.11)
Dyspnoea C4D1 -12.50  (4.25) 0.00 [1]   (NA)
Dyspnoea C5D1 -3.03  (6.55) NA [2]   (NA)
Dyspnoea C6D1 -2.78  (6.43) NA [2]   (NA)
Dyspnoea EoT -2.31  (3.09) 0.54  (3.95)
Insomnia C2D1 -2.40  (3.01) 1.59  (5.85)
Insomnia C3D1 -9.26  (3.38) 0.00  (19.25)
Insomnia C4D1 -7.50  (3.27) 0.00 [1]   (NA)
Insomnia C5D1 -4.55  (4.55) NA [2]   (NA)
Insomnia C6D1 -11.11  (9.48) NA [2]   (NA)
Insomnia EoT -2.31  (3.09) 0.00  (3.91)
Appetite Loss C2D1 -4.20  (2.83) 3.17  (7.24)
Appetite Loss C3D1 -8.33  (4.31) 0.00  (0.00)
Appetite Loss C4D1 -11.67  (5.54) 0.00 [1]   (NA)
Appetite Loss C5D1 -6.06  (7.80) NA [2]   (NA)
Appetite Loss C6D1 2.78  (9.59) NA [2]   (NA)
Appetite Loss EoT -1.32  (3.54) 11.83  (4.41)
Constipation C2D1 -1.21  (2.47) 0.00  (5.14)
Constipation C3D1 0.47  (3.44) 0.00  (0.00)
Constipation C4D1 -2.50  (3.66) 0.00 [1]   (NA)
Constipation C5D1 0.00  (5.37) NA [2]   (NA)
Constipation C6D1 5.56  (5.56) NA [2]   (NA)
Constipation EoT 2.64  (2.60) -0.54  (2.71)
Diarrhoea C2D1 -3.30  (2.17) -1.59  (4.87)
Diarrhoea C3D1 -5.09  (2.61) -11.11  (11.11)
Diarrhoea C4D1 -0.83  (3.27) 0.00 [1]   (NA)
Diarrhoea C5D1 -9.52  (4.68) NA [2]   (NA)
Diarrhoea C6D1 -2.78  (4.95) NA [2]   (NA)
Diarrhoea EoT 2.31  (1.89) 3.76  (3.35)
Financial Difficulties C2D1 -1.80  (1.99) 0.00  (8.72)
Financial Difficulties C3D1 0.47  (3.24) 0.00  (0.00)
Financial Difficulties C4D1 -1.67  (3.37) 0.00 [1]   (NA)
Financial Difficulties C5D1 -3.03  (3.74) NA [2]   (NA)
Financial Difficulties C6D1 -5.56  (3.75) NA [2]   (NA)
Financial Difficulties EoT 0.33  (3.09) 2.19  (2.80)
Fatigue C2D1 -4.10  (2.40) 5.82  (6.88)
Fatigue C3D1 -8.33  (3.02) 22.22  (6.42)
Fatigue C4D1 -9.17  (4.64) -11.11 [1]   (NA)
Fatigue C5D1 -7.32  (5.61) NA [2]   (NA)
Fatigue C6D1 0.00  (6.42) NA [2]   (NA)
Fatigue Eot -0.33  (2.66) 5.73  (3.27)
Nausea and Vomiting C2D1 0.15  (2.16) -0.79  (2.69)
Nausea and Vomiting C3D1 -4.63  (2.80) 0.00  (0.00)
Nausea and Vomiting C4D1 -3.33  (3.17) -16.67 [1]   (NA)
Nausea and Vomiting C5D1 2.27  (2.96) NA [2]   (NA)
Nausea and Vomiting C6D1 0.00  (2.90) NA [2]   (NA)
Nausea and Vomiting EoT -0.17  (2.33) 3.49  (2.43)
Pain C2D1 -8.86  (2.71) -7.14  (7.68)
Pain C3D1 -8.56  (3.73) -5.56  (14.70)
Pain C4D1 -4.17  (3.81) -33.33 [1]   (NA)
Pain C5D1 0.76  (7.48) NA [2]   (NA)
Pain C6D1 -2.78  (9.59) NA [2]   (NA)
Pain EoT -1.98  (2.88) -7.26  (3.75)
[1]
n=1
[2]
n=0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Physical Functioning
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0139
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 6.9
Confidence Interval (2-Sided) 95%
1.4 to 12.3
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Role Functioning
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0065
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 11.4
Confidence Interval (2-Sided) 95%
3.2 to 19.5
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Emotional Functioning
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3307
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.3
Confidence Interval (2-Sided) 95%
-6.9 to 2.3
Estimation Comments [Not Specified]
Show Statistical Analysis 4 Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Cognitive Functioning
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1904
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 2.8
Confidence Interval (2-Sided) 95%
-1.4 to 7.0
Estimation Comments [Not Specified]
Show Statistical Analysis 5 Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Social Functioning
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0336
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 8.4
Confidence Interval (2-Sided) 95%
0.7 to 16.1
Estimation Comments [Not Specified]
Show Statistical Analysis 6 Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Global Health Status
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1572
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.3
Confidence Interval (2-Sided) 95%
-1.7 to 10.3
Estimation Comments [Not Specified]
Show Statistical Analysis 7 Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Dyspnoea
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1281
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.7
Confidence Interval (2-Sided) 95%
-10.8 to 1.4
Estimation Comments [Not Specified]
Show Statistical Analysis 8 Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Insomnia
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6207
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.7
Confidence Interval (2-Sided) 95%
-8.7 to 5.2
Estimation Comments [Not Specified]
Show Statistical Analysis 9 Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Appetite Loss
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0193
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -8.7
Confidence Interval (2-Sided) 95%
-16.0 to -1.4
Estimation Comments [Not Specified]
Show Statistical Analysis 10 Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Constipation
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6249
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 1.4
Confidence Interval (2-Sided) 95%
-4.4 to 7.3
Estimation Comments [Not Specified]
Show Statistical Analysis 11 Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Diarrhoea
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1534
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -3.0
Confidence Interval (2-Sided) 95%
-7.2 to 1.1
Estimation Comments [Not Specified]
Show Statistical Analysis 12 Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Financial Difficulties
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4915
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -2.5
Confidence Interval (2-Sided) 95%
-9.7 to 4.7
Estimation Comments [Not Specified]
Show Statistical Analysis 13 Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Fatigue
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1789
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -4.4
Confidence Interval (2-Sided) 95%
-10.8 to 2.0
Estimation Comments [Not Specified]
Show Statistical Analysis 14 Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Nausea and Vomiting
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4578
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.6
Confidence Interval (2-Sided) 95%
-6.0 to 2.7
Estimation Comments [Not Specified]
Show Statistical Analysis 15 Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments Pain
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8428
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.7
Confidence Interval (2-Sided) 95%
-7.3 to 6.0
Estimation Comments [Not Specified]
10.Secondary Outcome
Title Change From Baseline in EuroQol 5 Dimension Health Questionnaire (EQ-5D) Index Score
Hide Description The EQ-5D self-report questionnaire is a standardized measure of health status developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), EQ-VAS. The EQ-5D descriptive system measures a participants’ health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting “no problems”, “some problems”, and “extreme problems”. The EQ-VAS records the respondent’s self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state. EQ-5D summary index is obtained with a formula that weights each level of the dimensions. The index-based score is interpreted along a continuum of 0 (death) to 1 (perfect health).
Time Frame Day 1 of each cycle prior to dosing and EoT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Although only 143 participants were treated in the Defined Investigator’s Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population.
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 164 162
Mean (Standard Error)
Unit of Measure: Score on a scale
Cycle 2, Day 1 0.00  (0.02) 0.02  (0.03)
Cycle 3, Day 1 0.01  (0.02) -0.08  (0.08)
Cycle 4, Day 1 0.04  (0.03) 0.00 [1]   (NA)
Cycle 5, Day 1 0.04  (0.04) NA [2]   (NA)
Cycle 6, Day 1 0.03  (0.04) NA [2]   (NA)
EoT -0.01  (0.02) -0.04  (0.02)
[1]
n=1
[2]
n=0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1710
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.01 to 0.07
Estimation Comments [Not Specified]
11.Secondary Outcome
Title Change From Baseline in EQ-5D VAS
Hide Description The EQ-5D self-report questionnaire is a standardized measure of health status developed by the EuroQoL Group. It consists of the EQ-5D descriptive system and a visual analogue scale (VAS), EQ-VAS. The EQ-5D descriptive system measures a participants’ health state on 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, reflecting “no problems”, “some problems”, and “extreme problems”. The EQ-VAS records the respondent’s self-rated health on a scale from 0 (worst imaginable health state) to 100 (best imaginable health state); higher scores indicate a better health state.
Time Frame Day 1 of each cycle prior to dosing and EoT
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
ITT population. Although only 143 participants were treated in the Defined Investigator’s Choice of Chemotherapy arm, all 162 randomized participants were included in the ITT population.
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 164 162
Mean (Standard Error)
Unit of Measure: Score on a scale
Cycle 2, Day 1 5.81  (2.14) 5.90  (4.21)
Cycle 3, Day 1 8.13  (2.53) 19.67  (17.80)
Cycle 4, Day 1 7.13  (3.37) 44.00 [1]   (NA)
Cycle 5, Day 1 7.62  (4.43) NA [2]   (NA)
Cycle 6, Day 1 15.09  (9.14) NA [2]   (NA)
EoT 4.62  (2.38) -0.52  (2.88)
[1]
n=1
[2]
n=0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Inotuzumab Ozogamicin, Defined Investigator’s Choice of Chemotherapy
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1172
Comments [Not Specified]
Method Mixed Models Analysis
Comments Treatment, time, treatment-by-time interaction, and baseline included as covariate.
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 4.6
Confidence Interval (2-Sided) 95%
-1.2 to 10.4
Estimation Comments [Not Specified]
12.Secondary Outcome
Title Percentage of Participants With Veno-Occlusive Liver Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) Following Post Study HSCT
Hide Description VOD/SOS was defined as the occurrence of 2 out of the following 3 clinical criteria: 1) total serum bilirubin level >34 micromoles per liter (μmol/L) (>2.0 milligrams per deciliter [mg/dL]), 2) an increase in liver size from baseline or development of right upper quadrant pain of liver origin and 3) sudden weight gain >2.5% (eg, within a 72 hour period) because of fluid accumulation in the weeks following infusion of study drug or chemotherapy, or HSCT conditioning/preparative therapy, or development of ascites not present at baseline following such exposures AND the absence of other explanations for these signs and symptoms, OR development of bilirubin elevation, weight gain, or hepatomegaly plus histologic abnormalities on liver biopsy demonstrating hepatocyte necrosis in zone 3 of the liver acinus, sinusoidal fibrosis, and centrilobular hemorrhage, with or without fibrosis of the terminal hepatic venules.
Time Frame Up to 2 years from randomization
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Participants in the Safety population with post-study HSCT. A site visit in July 2017 (after clinical database lock), confirmed a fourth case of VOD/SOS occurred in the Defined Investigators Choice of Chemotherapy arm in March 2013 (approximately 3 months after the last dose).This was not entered on the CRF and therefore, is not included below.
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description:
Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status).
Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
Overall Number of Participants Analyzed 79 35
Measure Type: Number
Unit of Measure: Percentage of Participants
22.8 8.6
Time Frame SAEs and non-serious AEs are summarized from Cycle 1 Day 1 up to 42 days after last dose, or any time after Cycle 1 Day1 (treatment-related).
Adverse Event Reporting Description An event may appear as both an AE & SAE. However, what is presented are distinct events. An event may be categorized as serious in 1 participant & non-serious in another participant, or 1 participant may have experienced both a serious & non-serious event. Events were reported up to at least 28 days after last dose.
 
Arm/Group Title Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Hide Arm/Group Description Participants were treated with inotuzumab ozogamicin at a starting dose of 1.8 mg/m^2 (according to body surface area) per cycle with a divided-dose regimen using 3 weekly administrations. Participants received 0.8 mg/m^2/cycle on Week 1 (Day 1), followed by 0.5 mg/m^2 on Week 2 (Day 8) and Week 3 (Day 15) of a 21-day cycle, and administered as an intravenous infusion over 60 minutes. For participants who achieved a CR or CRi, or to allow recovery from toxicity, the length of Cycle 1 could be extended up to 28 days (ie, 1 week treatment-free interval starting on Day 21). For participants who achieved CR or CRi, the inotuzumab ozogamicin dose administered on Week 1 was reduced to 0.5 mg/m^2 (for a total cycle dose of 1.5 mg/m^2/cycle) for Cycles 2 through 6 (maximum number of cycles permitted). For Cycles 2 through 6, the cycle length was 28 days for all participants (regardless of remission status). Participants received fludarabine, cytarabine, granulocyte-colony stimulating factor (FLAG), mitoxantrone + cytarabine (MXN/Ara-C), or high-dose cytarabine (HIDAC), according to the Investigator’s choice.
All-Cause Mortality
Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   85/164 (51.83%)   72/143 (50.35%) 
Blood and lymphatic system disorders     
Anaemia  1  1/164 (0.61%)  0/143 (0.00%) 
Febrile neutropenia  1  19/164 (11.59%)  27/143 (18.88%) 
Leukopenia  1  1/164 (0.61%)  0/143 (0.00%) 
Neutropenia  1  2/164 (1.22%)  0/143 (0.00%) 
Pancytopenia  1  0/164 (0.00%)  2/143 (1.40%) 
Thrombocytopenia  1  1/164 (0.61%)  1/143 (0.70%) 
Cardiac disorders     
Acute coronary syndrome  1  1/164 (0.61%)  0/143 (0.00%) 
Atrial fibrillation  1  1/164 (0.61%)  1/143 (0.70%) 
Cardiac arrest  1  1/164 (0.61%)  0/143 (0.00%) 
Cardiac failure congestive  1  1/164 (0.61%)  0/143 (0.00%) 
Left ventricular dysfunction  1  2/164 (1.22%)  0/143 (0.00%) 
Myocardial infarction  1  1/164 (0.61%)  0/143 (0.00%) 
Pericarditis  1  1/164 (0.61%)  0/143 (0.00%) 
Eye disorders     
Blindness unilateral  1  1/164 (0.61%)  0/143 (0.00%) 
Gastrointestinal disorders     
Abdominal pain  1  3/164 (1.83%)  1/143 (0.70%) 
Abdominal pain lower  1  1/164 (0.61%)  0/143 (0.00%) 
Abdominal pain upper  1  1/164 (0.61%)  0/143 (0.00%) 
Ascites  1  1/164 (0.61%)  0/143 (0.00%) 
Colitis ischaemic  1  1/164 (0.61%)  0/143 (0.00%) 
Diarrhoea  1  0/164 (0.00%)  1/143 (0.70%) 
Dysphagia  1  0/164 (0.00%)  1/143 (0.70%) 
Gastritis haemorrhagic  1  1/164 (0.61%)  0/143 (0.00%) 
Gastrointestinal haemorrhage  1  1/164 (0.61%)  0/143 (0.00%) 
Ileal perforation  1  0/164 (0.00%)  1/143 (0.70%) 
Intestinal ischaemia  1  1/164 (0.61%)  1/143 (0.70%) 
Intra-abdominal haemorrhage  1  1/164 (0.61%)  0/143 (0.00%) 
Large intestinal ulcer  1  1/164 (0.61%)  0/143 (0.00%) 
Lower gastrointestinal haemorrhage  1  1/164 (0.61%)  0/143 (0.00%) 
Mesenteric haemorrhage  1  1/164 (0.61%)  0/143 (0.00%) 
Nausea  1  2/164 (1.22%)  0/143 (0.00%) 
Oesophageal stenosis  1  0/164 (0.00%)  1/143 (0.70%) 
Pancreatitis  1  1/164 (0.61%)  0/143 (0.00%) 
Proctalgia  1  0/164 (0.00%)  1/143 (0.70%) 
Small intestinal obstruction  1  1/164 (0.61%)  0/143 (0.00%) 
Stomatitis  1  2/164 (1.22%)  1/143 (0.70%) 
Upper gastrointestinal haemorrhage  1  1/164 (0.61%)  0/143 (0.00%) 
Vomiting  1  1/164 (0.61%)  0/143 (0.00%) 
General disorders     
Asthenia  1  3/164 (1.83%)  0/143 (0.00%) 
Chest pain  1  1/164 (0.61%)  0/143 (0.00%) 
Disease progression  1  8/164 (4.88%)  5/143 (3.50%) 
Fatigue  1  1/164 (0.61%)  0/143 (0.00%) 
Mucosal inflammation  1  0/164 (0.00%)  1/143 (0.70%) 
Multiple organ dysfunction syndrome  1  2/164 (1.22%)  2/143 (1.40%) 
Pain  1  1/164 (0.61%)  0/143 (0.00%) 
Pyrexia  1  5/164 (3.05%)  3/143 (2.10%) 
Hepatobiliary disorders     
Cholecystitis  1  1/164 (0.61%)  0/143 (0.00%) 
Hepatic vein thrombosis  1  1/164 (0.61%)  0/143 (0.00%) 
Hyperbilirubinaemia  1  0/164 (0.00%)  3/143 (2.10%) 
Venoocclusive liver disease  1 [1]  23/164 (14.02%)  3/143 (2.10%) 
Infections and infestations     
Adenoviral upper respiratory infection  1  1/164 (0.61%)  0/143 (0.00%) 
Appendicitis  1  0/164 (0.00%)  1/143 (0.70%) 
Bacteraemia  1  3/164 (1.83%)  1/143 (0.70%) 
Bacterial infection  1  0/164 (0.00%)  1/143 (0.70%) 
Brain abscess  1  1/164 (0.61%)  0/143 (0.00%) 
Bronchopulmonary aspergillosis  1  0/164 (0.00%)  1/143 (0.70%) 
Candida infection  1  1/164 (0.61%)  1/143 (0.70%) 
Cellulitis  1  1/164 (0.61%)  1/143 (0.70%) 
Clostridium difficile colitis  1  2/164 (1.22%)  1/143 (0.70%) 
Clostridium difficile infection  1  1/164 (0.61%)  0/143 (0.00%) 
Corona virus infection  1  1/164 (0.61%)  0/143 (0.00%) 
Cytomegalovirus chorioretinitis  1  0/164 (0.00%)  1/143 (0.70%) 
Device related infection  1  1/164 (0.61%)  0/143 (0.00%) 
Diverticulitis  1  1/164 (0.61%)  0/143 (0.00%) 
Enteritis necroticans  1  0/164 (0.00%)  1/143 (0.70%) 
Enterococcal bacteraemia  1  1/164 (0.61%)  0/143 (0.00%) 
Enterococcal sepsis  1  1/164 (0.61%)  0/143 (0.00%) 
Escherichia bacteraemia  1  2/164 (1.22%)  2/143 (1.40%) 
Escherichia sepsis  1  1/164 (0.61%)  2/143 (1.40%) 
Febrile infection  1  1/164 (0.61%)  0/143 (0.00%) 
Fungaemia  1  1/164 (0.61%)  0/143 (0.00%) 
Fungal infection  1  1/164 (0.61%)  0/143 (0.00%) 
Herpes zoster  1  1/164 (0.61%)  0/143 (0.00%) 
Infection  1  1/164 (0.61%)  0/143 (0.00%) 
Influenza  1  2/164 (1.22%)  0/143 (0.00%) 
Klebsiella bacteraemia  1  0/164 (0.00%)  1/143 (0.70%) 
Klebsiella infection  1  0/164 (0.00%)  1/143 (0.70%) 
Liver abscess  1  0/164 (0.00%)  1/143 (0.70%) 
Lung infection  1  1/164 (0.61%)  2/143 (1.40%) 
Necrotising fasciitis fungal  1  0/164 (0.00%)  1/143 (0.70%) 
Neutropenic sepsis  1  3/164 (1.83%)  4/143 (2.80%) 
Parainfluenzae virus infection  1  1/164 (0.61%)  0/143 (0.00%) 
Pneumonia  1  10/164 (6.10%)  0/143 (0.00%) 
Pneumonia fungal  1  0/164 (0.00%)  3/143 (2.10%) 
Pneumonia pseudomonal  1  0/164 (0.00%)  1/143 (0.70%) 
Pseudomonal bacteraemia  1  1/164 (0.61%)  2/143 (1.40%) 
Pseudomonal sepsis  1  1/164 (0.61%)  0/143 (0.00%) 
Respiratory tract infection  1  1/164 (0.61%)  0/143 (0.00%) 
Sepsis  1  4/164 (2.44%)  10/143 (6.99%) 
Septic embolus  1  1/164 (0.61%)  0/143 (0.00%) 
Septic shock  1  3/164 (1.83%)  3/143 (2.10%) 
Serratia bacteraemia  1  1/164 (0.61%)  0/143 (0.00%) 
Sinusitis fungal  1  1/164 (0.61%)  0/143 (0.00%) 
Staphylococcal bacteraemia  1  1/164 (0.61%)  1/143 (0.70%) 
Staphylococcal sepsis  1  2/164 (1.22%)  1/143 (0.70%) 
Systemic candida  1  1/164 (0.61%)  1/143 (0.70%) 
Systemic mycosis  1  0/164 (0.00%)  1/143 (0.70%) 
Urinary tract infection  1  1/164 (0.61%)  1/143 (0.70%) 
Urinary tract infection fungal  1  1/164 (0.61%)  0/143 (0.00%) 
Mucormycosis  1  1/164 (0.61%)  0/143 (0.00%) 
Injury, poisoning and procedural complications     
Fall  1  1/164 (0.61%)  0/143 (0.00%) 
Subdural haematoma  1  1/164 (0.61%)  3/143 (2.10%) 
Metabolism and nutrition disorders     
Fluid overload  1  1/164 (0.61%)  0/143 (0.00%) 
Hyperglycaemia  1  2/164 (1.22%)  0/143 (0.00%) 
Lactic acidosis  1  1/164 (0.61%)  0/143 (0.00%) 
Tumour lysis syndrome  1  2/164 (1.22%)  0/143 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  1/164 (0.61%)  0/143 (0.00%) 
Back pain  1  2/164 (1.22%)  0/143 (0.00%) 
Bone infarction  1  1/164 (0.61%)  0/143 (0.00%) 
Neck pain  1  1/164 (0.61%)  0/143 (0.00%) 
Osteonecrosis  1  1/164 (0.61%)  0/143 (0.00%) 
Nervous system disorders     
Cerebrovascular accident  1  0/164 (0.00%)  1/143 (0.70%) 
Haemorrhage intracranial  1  1/164 (0.61%)  1/143 (0.70%) 
Headache  1  2/164 (1.22%)  0/143 (0.00%) 
Nervous system disorder  1  1/164 (0.61%)  1/143 (0.70%) 
Renal and urinary disorders     
Acute kidney injury  1  2/164 (1.22%)  0/143 (0.00%) 
Haematuria  1  1/164 (0.61%)  0/143 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Acute respiratory distress syndrome  1  1/164 (0.61%)  0/143 (0.00%) 
Epistaxis  1  0/164 (0.00%)  1/143 (0.70%) 
Pharyngeal stenosis  1  0/164 (0.00%)  1/143 (0.70%) 
Pleural effusion  1  1/164 (0.61%)  0/143 (0.00%) 
Respiratory failure  1  2/164 (1.22%)  6/143 (4.20%) 
Respiratory tract oedema  1  0/164 (0.00%)  1/143 (0.70%) 
Skin and subcutaneous tissue disorders     
Dermatitis allergic  1  1/164 (0.61%)  0/143 (0.00%) 
Vascular disorders     
Hypertension  1  0/164 (0.00%)  1/143 (0.70%) 
Hypotension  1  0/164 (0.00%)  3/143 (2.10%) 
Shock haemorrhagic  1  1/164 (0.61%)  0/143 (0.00%) 
Thrombophlebitis  1  0/164 (0.00%)  1/143 (0.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
[1]
After clinical database lock, a fourth case of VOD/SOS was confirmed in the Defined Investigators Choice of Chemotherapy arm in March 2013 (approximately 3 months after last dose). This was not entered on the CRF and therefore, is not included below.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Inotuzumab Ozogamicin Defined Investigator’s Choice of Chemotherapy
Affected / at Risk (%) Affected / at Risk (%)
Total   159/164 (96.95%)   143/143 (100.00%) 
Blood and lymphatic system disorders     
Anaemia  1  54/164 (32.93%)  79/143 (55.24%) 
Febrile neutropenia  1  27/164 (16.46%)  52/143 (36.36%) 
Leukopenia  1  47/164 (28.66%)  54/143 (37.76%) 
Lymphopenia  1  31/164 (18.90%)  36/143 (25.17%) 
Neutropenia  1  79/164 (48.17%)  66/143 (46.15%) 
Thrombocytopenia  1  80/164 (48.78%)  86/143 (60.14%) 
Cardiac disorders     
Tachycardia  1  6/164 (3.66%)  16/143 (11.19%) 
Eye disorders     
Dry eye  1  1/164 (0.61%)  8/143 (5.59%) 
Gastrointestinal disorders     
Abdominal distension  1  10/164 (6.10%)  2/143 (1.40%) 
Abdominal pain  1  19/164 (11.59%)  26/143 (18.18%) 
Abdominal pain upper  1  11/164 (6.71%)  12/143 (8.39%) 
Constipation  1  28/164 (17.07%)  34/143 (23.78%) 
Diarrhoea  1  30/164 (18.29%)  55/143 (38.46%) 
Dyspepsia  1  3/164 (1.83%)  9/143 (6.29%) 
Nausea  1  52/164 (31.71%)  68/143 (47.55%) 
Stomatitis  1  5/164 (3.05%)  9/143 (6.29%) 
Vomiting  1  25/164 (15.24%)  35/143 (24.48%) 
General disorders     
Asthenia  1  14/164 (8.54%)  14/143 (9.79%) 
Chest pain  1  3/164 (1.83%)  9/143 (6.29%) 
Chills  1  18/164 (10.98%)  17/143 (11.89%) 
Fatigue  1  41/164 (25.00%)  24/143 (16.78%) 
Mucosal inflammation  1  6/164 (3.66%)  19/143 (13.29%) 
Oedema peripheral  1  13/164 (7.93%)  13/143 (9.09%) 
Pain  1  12/164 (7.32%)  8/143 (5.59%) 
Pyrexia  1  49/164 (29.88%)  57/143 (39.86%) 
Hepatobiliary disorders     
Hyperbilirubinaemia  1  35/164 (21.34%)  23/143 (16.08%) 
Infections and infestations     
Bacteraemia  1  4/164 (2.44%)  13/143 (9.09%) 
Pneumonia  1  4/164 (2.44%)  12/143 (8.39%) 
Sinusitis  1  4/164 (2.44%)  8/143 (5.59%) 
Injury, poisoning and procedural complications     
Contusion  1  10/164 (6.10%)  3/143 (2.10%) 
Fall  1  11/164 (6.71%)  4/143 (2.80%) 
Investigations     
Alanine aminotransferase increased  1  25/164 (15.24%)  18/143 (12.59%) 
Aspartate aminotransferase increased  1  37/164 (22.56%)  16/143 (11.19%) 
Blood alkaline phosphatase increased  1  21/164 (12.80%)  10/143 (6.99%) 
Gamma-glutamyltransferase increased  1  35/164 (21.34%)  12/143 (8.39%) 
Lipase increased  1  15/164 (9.15%)  1/143 (0.70%) 
White blood cell count decreased  1  10/164 (6.10%)  9/143 (6.29%) 
Metabolism and nutrition disorders     
Decreased appetite  1  19/164 (11.59%)  18/143 (12.59%) 
Fluid overload  1  2/164 (1.22%)  8/143 (5.59%) 
Hyperglycaemia  1  11/164 (6.71%)  12/143 (8.39%) 
Hypoalbuminaemia  1  10/164 (6.10%)  7/143 (4.90%) 
Hypocalcaemia  1  11/164 (6.71%)  15/143 (10.49%) 
Hypokalaemia  1  25/164 (15.24%)  33/143 (23.08%) 
Hypomagnesaemia  1  10/164 (6.10%)  12/143 (8.39%) 
Hyponatraemia  1  5/164 (3.05%)  9/143 (6.29%) 
Hypophosphataemia  1  9/164 (5.49%)  10/143 (6.99%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  9/164 (5.49%)  7/143 (4.90%) 
Back pain  1  16/164 (9.76%)  10/143 (6.99%) 
Bone pain  1  3/164 (1.83%)  10/143 (6.99%) 
Pain in extremity  1  13/164 (7.93%)  16/143 (11.19%) 
Nervous system disorders     
Dizziness  1  12/164 (7.32%)  16/143 (11.19%) 
Headache  1  45/164 (27.44%)  38/143 (26.57%) 
Psychiatric disorders     
Anxiety  1  8/164 (4.88%)  11/143 (7.69%) 
Depression  1  4/164 (2.44%)  9/143 (6.29%) 
Insomnia  1  24/164 (14.63%)  22/143 (15.38%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  22/164 (13.41%)  23/143 (16.08%) 
Dyspnoea  1  10/164 (6.10%)  18/143 (12.59%) 
Epistaxis  1  24/164 (14.63%)  12/143 (8.39%) 
Oropharyngeal pain  1  6/164 (3.66%)  10/143 (6.99%) 
Pleural effusion  1  3/164 (1.83%)  8/143 (5.59%) 
Skin and subcutaneous tissue disorders     
Erythema  1  7/164 (4.27%)  9/143 (6.29%) 
Pruritus  1  8/164 (4.88%)  10/143 (6.99%) 
Rash  1  14/164 (8.54%)  27/143 (18.88%) 
Vascular disorders     
Hypertension  1  9/164 (5.49%)  8/143 (5.59%) 
Hypotension  1  12/164 (7.32%)  22/143 (15.38%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 18.1
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. Investigators will, on request, remove any previously undisclosed Confidential Information (other than the Study results themselves) before disclosure.
Results Point of Contact
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
Phone: 1-800-718-1021
Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01564784     History of Changes
Other Study ID Numbers: B1931022
2011-005491-41 ( EudraCT Number )
First Submitted: March 26, 2012
First Posted: March 28, 2012
Results First Submitted: March 2, 2017
Results First Posted: January 17, 2018
Last Update Posted: January 17, 2018