A Study Of Inotuzumab Ozogamicin Plus Rituximab For Relapsed/Refractory Aggressive Non-Hodgkin Lymphoma Patients Who Are Not Candidates For Intensive High-Dose Chemotherapy

• ClinicalTrials.gov Identifier: NCT01232556
• Recruitment Status: Terminated
• First Posted: November 2, 2010
• Results First Posted: August 21, 2018
• Last Update Posted: January 8, 2019
• Sponsor: Pfizer
• Collaborator: UCB Pharma
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: October 27, 2010
• First Posted Date: November 2, 2010
• Results First Submitted Date: July 17, 2017
• Results First Posted Date: August 21, 2018
• Last Update Posted Date: January 8, 2019
• Actual Study Start Date: April 4, 2011
• Actual Primary Completion Date: March 28, 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (submitted: October 29, 2010): Overall Survival [ Time Frame: 5 years ]

Current Secondary Outcome Measures (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 (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: 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: 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: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Lymphoma, Non-Hodgkin

Intervention

• 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

• 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

Recruitment Information

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

Eligibility Criteria

Inclusion Criteria:

-

Exclusion Criteria:

-

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: 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: NCT01232556
• Other Study ID Numbers: 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

• 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: Pfizer
• Collaborators: UCB Pharma

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: December 2018