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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

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.

Condition or disease Intervention/treatment Phase
Lymphoma, Non-Hodgkin Drug: Inotuzumab ozogamicin Drug: Rituximab Drug: rituximab + gemcitabine Drug: rituximab +bendamustine Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 338 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 4, 2011
Actual Primary Completion Date : March 28, 2014
Actual Study Completion Date : March 28, 2014


Arm Intervention/treatment
Experimental: 1
Inotuzumab ozogamicin+rituximab
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

Active Comparator: 2
Investigator's choice of (1) rituximab+gemcitabine, or (2) rituximab+bendamustine
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




Primary Outcome Measures :
  1. 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.

  2. 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..


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.


  4. 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.

  5. 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.

  6. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

-

Exclusion Criteria:

-


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01232556


Locations
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Sponsors and Collaborators
Pfizer
UCB Pharma
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01232556    
Other Study ID Numbers: B1931008
3129K5-3303 ( Other Identifier: Alias Study Number )
2010-020147-12 ( EudraCT Number )
First Posted: November 2, 2010    Key Record Dates
Results First Posted: August 21, 2018
Last Update Posted: January 8, 2019
Last Verified: December 2018
Individual Participant Data (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
Keywords provided by Pfizer:
inotuzumab ozogamicin
aggressive Non-Hodgkin lymphoma
diffuse large b-cell lymphoma
relapsed/refractory lymphoma
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Aggression
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Behavioral Symptoms
Gemcitabine
Rituximab
Bendamustine Hydrochloride
Inotuzumab Ozogamicin
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Antineoplastic Agents, Alkylating
Alkylating Agents