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Trial record 1 of 1 for:    NCT01232556
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A Study Of Inotuzumab Ozogamicin Plus Rituximab For Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy

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ClinicalTrials.gov Identifier: NCT01232556
Recruitment Status : Terminated (The study was terminated prematurely on May 16, 2013, for futility. No new or unexpected safety issues were identified.)
First Posted : November 2, 2010
Results First Posted : August 21, 2018
Last Update Posted : January 8, 2019
Sponsor:
Collaborator:
UCB Pharma
Information provided by (Responsible Party):
Pfizer

Tracking Information
First Submitted Date  ICMJE October 27, 2010
First Posted Date  ICMJE November 2, 2010
Results First Submitted Date  ICMJE July 17, 2017
Results First Posted Date  ICMJE August 21, 2018
Last Update Posted Date January 8, 2019
Actual Study Start Date  ICMJE April 4, 2011
Actual Primary Completion Date March 28, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 24, 2018)
  • Overall Survival [ Time Frame: From randomization up to 5 years after last dose or up to final study visit, whichever occurs first. ]
    Overall Survival (OS) was defined as the time from randomization to death due to any cause, censoring at the date of last contact or the end of the study. The Kaplan-Meier method was used to determine OS. The hazard ratio and corresponding 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
  • Percentage of Participants With a Treatment Emergent Adverse Event (TEAE) (Safety Population) [ Time Frame: Up to 20 weeks after the first dose of study drug ]
    Includes all TEAEs: Any event that occurred after the first dose of study drug and was not present prior to study drug administration or worsened in severity after study drug administration..
Original Primary Outcome Measures  ICMJE
 (submitted: October 29, 2010)
Overall Survival [ Time Frame: 5 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 24, 2018)
  • Progression-Free Survival (PFS) [ Time Frame: From randomization up to 2 years or final study visit, whichever occurs first, including but not limited to planned assessments scheduled approximately every 12 weeks. ]
    PFS is defined as time from date of randomization to date of progressive disease (PD, including investigator's claim of clinical progression), date of death from any cause, or initiation of a new treatment for the lymphoma due to persistent/refractory disease. The Kaplan-Meier method was used to determine PFS. The hazard ratio and corresponding 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression. PD requires the following:
    1. Appearance of any new lesion more than 1.5 cm in any axis during or at the end of treatment, even if other lesions are decreasing in size.
    2. At least a 50% increase from nadir in the sum of the product diameters of any previously involved nodes, or in a single involved node, or the size of other lesions.
    3. At least a 50% increase in the longest diameter of any single previously identified node more than 1 cm in its short axis.
  • Percentage of Participants With A Best Overall Response of CR or Partial Response (PR) Per NCI International Response Criteria for NHL [ Time Frame: Up to 2 years from first study drug dose or up to final study visit, whichever occurs first, including but not limited to planned assessments scheduled approximately every 12 weeks. ]
    CR is defined as disappearance of all detectable clinical evidence of disease (including cleared infiltrate on repeat bone marrow aspirate/biopsy if lymphoma involvement of bone marrow before treatment). Partial Response (PR) requires the following:
    1. ≥50 % decrease in SPD of the six largest dominant nodes or nodal masses.
    2. No increase in the size of other nodes, liver, or spleen.
    3. Splenic and hepatic nodules must regress by ≥50% in the SPD, or for single nodules, in the greatest transverse diameter.
    4. With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.
    5. No new sites of disease. The 95% CI was determined using the exact method based on binomial distribution.
  • Percentage of Participants With A Best Overall Response of CR, Unconfirmed CR (unCR), PR, or Unconfirmed PR (unPR) Per NCI International Response Criteria for NHL [ Time Frame: Up to 2 years from first study drug dose or up to final study visit, whichever occurs first, including but not limited to planned assessments scheduled approximately every 12 weeks. ]
    CR is defined as disappearance of all detectable clinical evidence of disease (including cleared infiltrate on repeat bone marrow aspirate/biopsy if lymphoma involvement of bone marrow before treatment). Partial Response (PR) requires the following:
    1. ≥50 % decrease in SPD of the six largest dominant nodes or nodal masses.
    2. No increase in the size of other nodes, liver, or spleen.
    3. Splenic and hepatic nodules must regress by ≥50% in the SPD, or for single nodules, in the greatest transverse diameter.
    4. With the exception of splenic and hepatic nodules, involvement of other organs is usually assessable and no measurable disease should be present.
    5. No new sites of disease. unCR and unPR means didn't have confirmatory assessment (including bone marrow assessment for CR).
    The 95% CI was determined using the exact method based on binomial distribution.
  • Duration of Response [ Time Frame: Up to 2 years from first study drug dose or up to final study visit, whichever occurs first, including but not limited to planned assessments scheduled approximately every 12 weeks. ]
    The duration of overall response is measured from the first date of response until the first date that the progressive disease (PD) or death is objectively documented. The hazard ratio and corresponding 95% 2-sided confidence interval were calculated using stratified Cox proportional hazard regression.
  • Health Status as Assessed by the European Quality of Life 5 Dimension (EQ-5D) Questionnaire [ Time Frame: Assessed at Day 1 of each cycle and 6-9 weeks after the last dose, Cycle 3 (Week 12) reported ]
    EQ-5D consists of a descriptive system and an EQ visual analogue scale. The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 3 levels: no problems, some problems, extreme problems. The scale, the best state is marked 100 and the worst state is marked 0, is to help the participant to say how good or bad a health state is. EQ-5D index, which was reported, was derived based on US weight. The range of EQ-5D index is -0.109 to 1.00. Higher scores mean better outcomes. The average post-baseline scores for EQ-5D index were computed at approximately Week 12. The overall treatment comparisons were estimated at approximately Week 12.
  • Health Related Quality of Life as Assessed by the Functional Assessment of Cancer Therapy for Lymphoma (FACT-Lym) Questionnaire [ Time Frame: Assessed at Day 1 of each cycle and 6-9 weeks after the last dose, Cycle 3 (Week 12) reported ]
    FACT-Lym is a questionnaire that begins with 27 items covering four core Health-Related Quality of Life subscales: Physical Well-being (7 items), Social/Family Well-being (7), Emotional Well-being (6), and Functional Well-being (7). The FACT-Lym also includes an additional concerns subscale (15 items). It also asks participants about their concerns about lumps and swelling, fevers, infections, weight, appetite, emotional stability and treatment. The participants were requested to circle one number on a 0 to 4 points scale per line to indicate how true each statement has been for him/her during the past 7 days. FACT-Lym total score, which was reported, was derived based on FACT-Lym scoring guideline (Version 4). The range of FACT-Lym total score is 0 to 168. Higher scores mean better outcomes. The average post-baseline FACT-Lym total scores were computed at approximately Week 12. The overall treatment comparisons were estimated at approximately Week 12.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 29, 2010)
  • Safety and Tolerability: incidence of adverse events by treatment arm. [ Time Frame: ~every 6 months ]
  • Efficacy: overall response rate, progression free survival, duration of response [ Time Frame: at ~3 to 6 months after start of treatment, and ~2 years after start of treatment ]
  • Patient-reported health-related quality of life [ Time Frame: approximately 3 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 Plus Rituximab For Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy
Official Title  ICMJE AN OPEN-LABEL, RANDOMIZED, PHASE 3 STUDY OF INOTUZUMAB OZOGAMICIN ADMINISTERED IN COMBINATION WITH RITUXIMAB COMPARED TO DEFINED INVESTIGATOR'S CHOICE THERAPY IN SUBJECTS WITH RELAPSED OR REFRACTORY CD22-POSITIVE AGGRESSIVE NON-HODGKIN LYMPHOMA WHO ARE NOT CANDIDATES FOR INTENSIVE HIGH-DOSE CHEMOTHERAPY
Brief Summary The purpose of this study is to evaluate the efficacy of inotuzumab ozogamicin plus rituximab in relapsed/refractory aggressive Non-Hodgkin lymphoma patients who are not candidates for intensive high-dose chemotherapy. Specifically, the goal is to demonstrate the superiority of this combination compared with an active comparator arm (investigator's choice of rituximab+bendamustine or rituximab+gemcitabine) using the primary endpoint of overall survival.
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 Lymphoma, Non-Hodgkin
Intervention  ICMJE
  • Drug: Inotuzumab ozogamicin
    1.8 mg/m2 on day 2 every 28 days by IV infusion, 3 to 6 cycles
    Other Name: CMC-544
  • Drug: Rituximab
    375 mg/m2 on day 1 every 28 days by IV infusion, 3 to 6 cycles
  • Drug: rituximab + gemcitabine
    rituximab 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2 to 6, every 28 days by IV infusion, 3 to 6 cycles; gemcitabine 1000 mg/m2 on days 1, 8, and 15 every 28 days, 3 to 6 cycles
  • Drug: rituximab +bendamustine
    rituximab 375 mg/m2 on day 1 every 28 days by IV infusion, 3 to 6 cycles; bendamustine 120 mg/m2 on days 1 and 2 by IV infusion every 28 days, 3 to 6 cycles
Study Arms  ICMJE
  • Experimental: 1
    Inotuzumab ozogamicin+rituximab
    Interventions:
    • Drug: Inotuzumab ozogamicin
    • Drug: Rituximab
  • Active Comparator: 2
    Investigator's choice of (1) rituximab+gemcitabine, or (2) rituximab+bendamustine
    Interventions:
    • Drug: rituximab + gemcitabine
    • Drug: rituximab +bendamustine
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: July 24, 2018)
338
Original Estimated Enrollment  ICMJE
 (submitted: October 29, 2010)
377
Actual Study Completion Date  ICMJE March 28, 2014
Actual Primary Completion Date March 28, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

-

Exclusion Criteria:

-

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 Belgium,   Bulgaria,   Canada,   Croatia,   Czechia,   France,   Germany,   Hungary,   India,   Ireland,   Japan,   Lithuania,   Mexico,   Poland,   Puerto Rico,   Russian Federation,   Singapore,   Slovakia,   Spain,   Sweden,   Taiwan,   Thailand,   Ukraine,   United Kingdom,   United States
Removed Location Countries Czech Republic,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT01232556
Other Study ID Numbers  ICMJE B1931008
3129K5-3303 ( Other Identifier: Alias Study Number )
2010-020147-12 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
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