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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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
Inotuzumab Ozogamicin 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).
Defined Investigator’s Choice of Chemotherapy 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.

Participant Flow:   Overall Study
    Inotuzumab Ozogamicin   Defined Investigator’s Choice of Chemotherapy
STARTED   164 [1]   143 [2] 
COMPLETED   30   10 
NOT COMPLETED   134   133 
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)



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Inotuzumab Ozogamicin 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).
Defined Investigator’s Choice of Chemotherapy 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 Total of all reporting groups

Baseline Measures
   Inotuzumab Ozogamicin   Defined Investigator’s Choice of Chemotherapy   Total 
Overall Participants Analyzed 
[Units: Participants]
 164   143   307 
Age 
[Units: Years]
Mean (Standard Deviation)
 45.9  (17.07)   45.6  (16.32)   45.7  (16.70) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      73  44.5%      51  35.7%      124  40.4% 
Male      91  55.5%      92  64.3%      183  59.6% 


  Outcome Measures

1.  Primary:   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 ]

2.  Primary:   Overall Survival (OS)   [ Time Frame: Up to 5 years after randomization or 2 years from randomization of the last participant, whichever occurs first. ]

3.  Secondary:   Duration of Remission (DoR) for Participants Who Achieved CR/CRi (Per Investigator Assessment)   [ Time Frame: Up to 2 years from randomization ]

4.  Secondary:   Progression-Free Survival (PFS)   [ Time Frame: Up to 2 years from randomization ]

5.  Secondary:   Percentage of Participants Who Had a Hematopoietic Stem-Cell Transplant (HSCT)   [ Time Frame: Up to 19 weeks from last dose ]

6.  Secondary:   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 ]

7.  Secondary:   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 ]

8.  Secondary:   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 ]

9.  Secondary:   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 ]

10.  Secondary:   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 ]

11.  Secondary:   Change From Baseline in EQ-5D VAS   [ Time Frame: Day 1 of each cycle prior to dosing and EoT ]

12.  Secondary:   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 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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 agreement is:
unchecked 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. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked 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 more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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