A Study Of Inotuzumab Ozogamicin Plus Rituximab For Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy
- Conditions
- Lymphoma, Non-Hodgkin
- Interventions
- Registration Number
- NCT01232556
- Lead Sponsor
- Pfizer
- 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 available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 338
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 2 rituximab +bendamustine Investigator's choice of (1) rituximab+gemcitabine, or (2) rituximab+bendamustine 2 rituximab + gemcitabine Investigator's choice of (1) rituximab+gemcitabine, or (2) rituximab+bendamustine 1 Rituximab Inotuzumab ozogamicin+rituximab 1 Inotuzumab ozogamicin Inotuzumab ozogamicin+rituximab
- Primary Outcome Measures
Name Time Method Overall Survival 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) 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..
- Secondary Outcome Measures
Name Time Method Progression-Free Survival (PFS) 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 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 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 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 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 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.
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Trial Locations
- Locations (168)
Disney Family Cancer Center at Providence St Joseph Medical Center
🇺🇸Burbank, California, United States
Providence St Joseph Medical Center
🇺🇸Burbank, California, United States
Hematology-Oncology Medical Group of Fresno Inc
🇺🇸Fresno, California, United States
Ronald Reagan UCLA Medical Center Drug Information Center Department of Pharmaceutical Services
🇺🇸Los Angeles, California, United States
Clinical Research Unit
🇺🇸Los Angeles, California, United States
Peter Morton Medical Plaza
🇺🇸Los Angeles, California, United States
Ronald Reagan UCLA Medical Center
🇺🇸Los Angeles, California, United States
Sansum Clinic
🇺🇸Solvang, California, United States
UCLA Santa Monica Hematology Oncology
🇺🇸Santa Monica, California, United States
Howard University Hospital
🇺🇸Washington, District of Columbia, United States
Scroll for more (158 remaining)Disney Family Cancer Center at Providence St Joseph Medical Center🇺🇸Burbank, California, United States