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Trial record 1 of 1 for:    NCT01564784
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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 9, 2019
Sponsor:
Collaborator:
UCB Pharma
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE March 26, 2012
First Posted Date  ICMJE March 28, 2012
Results First Submitted Date  ICMJE March 2, 2017
Results First Posted Date  ICMJE January 17, 2018
Last Update Posted Date January 9, 2019
Actual Study Start Date  ICMJE August 2, 2012
Actual Primary Completion Date March 8, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
  • Percentage of Participants With Hematologic Remission (Complete Remission [CR]/Complete Remission With Incomplete Hematologic Recovery [CRi]) as Assessed by the Endpoint Adjudication Committee (EAC) [ 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 ]
    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.
  • Overall Survival (OS) [ Time Frame: Up to 5 years after randomization or 2 years from randomization of the last participant, whichever occurs first. ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 26, 2012)
Response to therapy (percentage of patients achieving a complete response and complete response with incomplete platelet and/or neutrophil recovery). [ Time Frame: 6 months ]
Change History Complete list of historical versions of study NCT01564784 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2017)
  • Duration of Remission (DoR) for Participants Who Achieved CR/CRi (Per Investigator Assessment) [ Time Frame: Up to 2 years from randomization ]
    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.
  • Progression-Free Survival (PFS) [ Time Frame: Up to 2 years from randomization ]
    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.
  • Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT) [ Time Frame: Up to 19 weeks from last dose ]
    HSCT rate was defined as the percentage of participants who underwent SCT following treatment with inotuzumab ozogamicin or Investigator's choice of chemotherapy.
  • Percentage of Participants Achieving MRD Negativity (Based on Central Laboratory Analysis) in Participants Achieving a CR/CRi (Per EAC Assessment) [ Time Frame: Up to approximately 4 weeks (EoT) from last dose of study drug ]
    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.
  • Cytogenetic Status (Based on Local Laboratory Analysis) of Participants With CR/CRi (Per EAC Assessment) [ Time Frame: Up to approximately 4 weeks (EoT) from last dose of study drug ]
    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.
  • Maximum Observed Inotuzumab Ozogamicin Serum Concentration (Cmax) and Pre-Dose Inotuzumab Ozogamicin Serum Concentration (Ctrough) Following Single and Multiple Dosing [ Time Frame: Days 1, 4, 8, and 15 of Cycle 1, Days 1 and 8 of Cycle 2 and Day 1 of Cycle 4 ]
    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).
  • Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Core 30 (EORTC QLQ-C30) Score [ Time Frame: Day 1 of each cycle prior to dosing and EoT ]
    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.
  • Change From Baseline in EuroQol 5 Dimension Health Questionnaire (EQ-5D) Index Score [ Time Frame: Day 1 of each cycle prior to dosing and EoT ]
    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).
  • Change From Baseline in EQ-5D VAS [ Time Frame: Day 1 of each cycle prior to dosing and EoT ]
    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.
  • Percentage of Participants With Veno-Occlusive Liver Disease (VOD)/Sinusoidal Obstruction Syndrome (SOS) Following Post Study HSCT [ Time Frame: Up to 2 years from randomization ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 26, 2012)
  • Overall Survival [ Time Frame: Baseline to 24 months ]
  • Progression free survival [ Time Frame: Baseline to 24 months ]
  • Volume of distribution (Vd) for inotuzumab ozogamicin in serum [ Time Frame: Cycle 1, Days 1, 3, 8 and 15; Cycle 2 , Days 1 and 8; Cycle 4, Days 1 and 8 ]
  • Systemic clearance (CL) for inotuzumab ozogamicin in serum [ Time Frame: Cycle 1, Days 1, 3, 8 and 15; Cycle 2 , Days 1 and 8; Cycle 4, Days 1 and 8 ]
  • Duration of response [ Time Frame: Baseline to 24 months ]
  • Rate of stem-cell transplantation: percentage of patients having stem-cell transplant [ Time Frame: Baseline to 8 months ]
  • Minimal residual disease (MRD): number of leukemic cells in bone marrow after CR/CRi [ Time Frame: Baseline to 7 months ]
  • Cytogenetics: quantitate t(9;22), MLL, and IGH rearrangements in leukemia cells [ Time Frame: Baseline to 7 months ]
  • Quality of life: . EORTC QLQ-C30 = European Organization for Research and Treatment of Cancer. Quality of Life Questionnaire, Core-30 [ Time Frame: Baseline to 6 months ]
  • Quality of life: EQ-5D = EuroQual -5D Health Questionnaire [ Time Frame: Baseline to 6 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Of Inotuzumab Ozogamicin Versus Investigator's Choice Of Chemotherapy In Patients With Relapsed Or Refractory Acute Lymphoblastic Leukemia
Official Title  ICMJE AN OPEN-LABEL, RANDOMIZED PHASE 3 STUDY OF INOTUZUMAB OZOGAMICIN COMPARED TO A DEFINED INVESTIGATOR'S CHOICE IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY CD22-POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA (ALL)
Brief Summary This study will compare the efficacy, in terms of complete responses and overall survival, of inotuzumab ozogamicin versus investigator's choice of chemotherapy.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • Drug: inotuzumab ozogamicin
    Dose: inotuzumab ozogamicin 0.8-0.5 mg/m^2 IV, weekly, 3 times per cycle Cycle length: 21-28 days Total number of cycles: 6
  • Drug: FLAG (fludarabine, cytarabine and G-CSF)
    Dose: cytarabine 2.0 g/m^2/day IV days 1-6 fludarabine30 mg/m^2/day IV days 2-6 Cycle length: 28 days Total number of cycles: 4
  • Drug: HIDAC (high dose cytarabine)
    cytarabine 3 g/m^2 IV every 12 hours for up to 12 times
  • Drug: cytarabine and mitoxantrone
    mitoxantrone 12 mg/m^2 IV days 1-3 cytarabine 200 mg/m^2/day IV over 7 days cycle length: 15-20 days Total number of cycles: 4
Study Arms  ICMJE
  • Experimental: Arm A
    Intervention: Drug: inotuzumab ozogamicin
  • Active Comparator: Arm B
    Interventions:
    • Drug: FLAG (fludarabine, cytarabine and G-CSF)
    • Drug: HIDAC (high dose cytarabine)
    • Drug: cytarabine and mitoxantrone
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: December 20, 2018)
326
Original Estimated Enrollment  ICMJE
 (submitted: March 26, 2012)
292
Actual Study Completion Date  ICMJE January 4, 2017
Actual Primary Completion Date March 8, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • CD22 expression
  • Adequate liver and renal functions

Exclusion Criteria:

  • Isolated extramedullary disease
  • Active Central Nervous System [CNS] disease
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Canada,   China,   Czechia,   Finland,   France,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Poland,   Singapore,   Spain,   Sweden,   Taiwan,   United Kingdom,   United States
Removed Location Countries Belgium,   Brazil,   Croatia,   Czech Republic,   Serbia,   Slovakia
 
Administrative Information
NCT Number  ICMJE NCT01564784
Other Study ID Numbers  ICMJE B1931022
2011-005491-41 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Responsible Party Pfizer
Study Sponsor  ICMJE Pfizer
Collaborators  ICMJE UCB Pharma
Investigators  ICMJE
Study Director: Pfizer CT.gov Call Center Pfizer
PRS Account Pfizer
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP