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A Study Comparing Maintenance Subcutaneous Rituximab With Observation Only in Participants With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma Who Had Responded to Rituximab-based Immunochemotherapy Induction and 2-year Maintenance With Subcutaneous Rituximab (MabCute)

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ClinicalTrials.gov Identifier: NCT01461928
Recruitment Status : Completed
First Posted : October 28, 2011
Results First Posted : August 6, 2019
Last Update Posted : August 6, 2019
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Tracking Information
First Submitted Date  ICMJE October 19, 2011
First Posted Date  ICMJE October 28, 2011
Results First Submitted Date  ICMJE May 31, 2019
Results First Posted Date  ICMJE August 6, 2019
Last Update Posted Date August 6, 2019
Actual Study Start Date  ICMJE December 20, 2011
Actual Primary Completion Date June 2, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
Maintenance II: Progression-free Survival (PFS) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia [ Time Frame: From randomization (Maintenance II) up to disease progression or death, whichever occurs first (up to approximately 24 months) ]
Progression free survival from randomization (PFSrand) is defined as the time from date of randomization to the date of first documented disease progression or death, whichever occurs first. One participant died in Induction before randomization and one participant died in Maintenance II Observation arm due to an SAE and were not considered in the analysis as no death page was completed. The Observation arm did not include one participant with AE outcome of death reported retrospectively 2 months after discontinuation from study (censored as having no event on Day 456 post-randomization).
Original Primary Outcome Measures  ICMJE
 (submitted: October 26, 2011)
Progression-free survival (Maintenance II phase): from randomization to disease progression or death; tumour assessments according to the revised International Working Group response (Cheson) criteria for lymphoma [ Time Frame: approximately 24 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 16, 2019)
  • Number of Participants With Adverse Events (AEs), Serious AEs, and Infusion/Administration-related Reactions (IRRs/ARRs) [ Time Frame: From day of first rituximab induction dose up to day of disease progression, or discontinuation of treatment for any reason (up to approximately 87 months) ]
    An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events. Not all AEs were followed up for the randomized Observation arm. Only Serious AEs and AE grade 3-5 (obtained retrospectively) were collected for this arm. Therefore arms are not comparable overall.
  • Event-free Survival (Time to Treatment Failure) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia [ Time Frame: From day of first rituximab induction dose up to day of any treatment failure, including disease progression, or discontinuation of treatment for any reason (up to approximately 87 months) ]
    Event-Free Survival was measured from the day of first rituximab Induction dose through Maintenance I and Maintenance II rituximab arm until the date of any treatment failure, including disease progression, or discontinuation of treatment for any reason (e.g. disease progression, toxicity, patient preference, initiation of new anti-lymphoma treatment, or death). Treatment discontinuation was considered as an event and was not applicable to the randomized observation arm.
  • Time to Next Lymphoma Treatment (TNLT) [ Time Frame: From day of first rituximab induction dose up to any new lymphoma treatment (up to approximately 87 months) ]
    Time to next lymphoma treatment (TNLT) is defined as the time from date of first rituximab induction dose to the date date of first documented intake of any new antilymphoma treatment (chemotherapy, radiotherapy, immunotherapy, etc.).
  • Overall Survival [ Time Frame: From day of first rituximab induction dose up to death (up to approximately 87 months) ]
    Overall survival from first induction treatment (OSRegist) is defined as the time from date of first rituximab induction dose to the date of death, irrespective of cause. One participant died in Induction before randomization and one participant died in Maintenance II Observation arm due to an SAE and were not considered in the analysis as no death page was completed.
  • Maintenance II: Overall Survival [ Time Frame: From randomization (Maintenance II) up to death (up to approximately 24 months) ]
    Overall survival from randomization (OSrand) is defined as the time from date of randomization to the date of death, irrespective of cause.
  • Percentage of Participants With Partial or Complete Tumor Response (PR/CR) Assessment at End of Induction Using 1999 International Working Group Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia [ Time Frame: From day of first rituximab induction dose up to end of induction period (up to approximately 8 months) ]
    Overall response rate is defined as the proportion of responders at the end of the Induction period. A responder is defined as a participant experiencing either CR or PR tumor response according to the Cheson response criteria for indolent lymphoma or the recommendations for Waldenström's macroglobulinemia.
  • Maintenance I: Percentage of Participants With Conversion of PR to CR Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia [ Time Frame: From day of first rituximab induction dose up to end of Maintenance I period (up to approximately 32 months) ]
  • Progression-free Survival (PFS) Using 1999 International Working Group (Cheson) Response Criteria for Lymphoma or by the Recommendations for Waldenström's Macroglobulinemia [ Time Frame: From day of first rituximab induction dose up to disease progression or death, whichever occurs first (up to approximately 87 months) ]
    Progression free survival from first induction treatment (PFSregist) is defined as the time from date of first rituximab induction dose to the date of first documented disease progression or death by any cause, whichever occurs first.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 26, 2011)
  • Safety: Incidence of adverse events [ Time Frame: approximately 6 years ]
  • Event-free survival (time to treatment failure): from day of first rituximab induction dose to day of any treatment failure, including disease progression, or discontinuation of treatment for any reason [ Time Frame: approximately 6 years ]
  • Time to next lymphoma treatment: from day of first rituximab induction dose to any new lymphoma treatment [ Time Frame: approximately 6 years ]
  • Overall survival [ Time Frame: approximately 6 years ]
  • Overall Response Rate [ Time Frame: approximately 6 years ]
  • Partial Response to Complete Response conversion rate (Induction and Maintenance I phase) [ Time Frame: approximately 6 years ]
  • Progression-free survival: from day of first induction dose until disease progression or death by any cause [ Time Frame: approximately 6 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study Comparing Maintenance Subcutaneous Rituximab With Observation Only in Participants With Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma Who Had Responded to Rituximab-based Immunochemotherapy Induction and 2-year Maintenance With Subcutaneous Rituximab
Official Title  ICMJE A Randomized Study Comparing Maintenance Therapy With Subcutaneous Rituximab Continued Until Progression With Observation Only in Patients With Relapsed or Refractory, Indolent Non-Hodgkin's Lymphoma Who Completed and Responded to Rituximab-based Immunochemotherapy Induction and Initial 2-year Rituximab Maintenance Therapy Administered Subcutaneously
Brief Summary This multicenter, randomized, open-label, parallel-group study will evaluate the efficacy and safety of subcutaneously administered rituximab in comparison with observation only as maintenance therapy in participants with relapsed or refractory indolent Non-Hodgkin's lymphoma (NHL). All participants will receive induction therapy with rituximab (375 milligrams per square meter [mg/m^2] intravenously [IV] in Cycle 1, then 1400 mg subcutaneous [SC] every 3-4 weeks) plus standard chemotherapy for 6-8 months; followed by 24 months of maintenance I period with rituximab (1400 mg SC every 8 weeks). Participants completing therapy and showing partial or complete response will be randomized to receive either rituximab (1400 mg SC every 8 weeks) or observation with no treatment during maintenance II period and will be followed for at least 15 months. Anticipated time on study treatment is until disease progression, unacceptable toxicity or end of study, whichever occurs first.
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 Non-Hodgkin's Lymphoma
Intervention  ICMJE
  • Drug: Chemotherapy (Induction Period)
    Participants will receive standard combination chemotherapy every 3-4 weeks for 6 to 8 months. The chemotherapy regimen will be selected at Investigator's discretion, for individual participant. Study protocol does not enforce any particular chemotherapy regimen.
  • Drug: Rituximab
    Participants will receive rituximab according to the regimen specified in individual arm.
    Other Names:
    • Rituxan
    • MabThera
    • RO0452294
Study Arms  ICMJE
  • Maintenance II Period Observation Only
    Participants will receive standard chemotherapy regimen in combination with 375 mg/m^2 rituximab IV in Cycle 1 (3-4 week-cycles), followed by 1400 mg rituximab SC every 3-4 weeks for 8 cycles (induction period); 1400 mg rituximab SC every 8 weeks for 24 months (Maintenance I period); no treatment in Maintenance II period until disease progression or end of study, whichever occurs first.
    Interventions:
    • Drug: Chemotherapy (Induction Period)
    • Drug: Rituximab
  • Experimental: Maintenance II Period Rituximab
    Participants will receive standard chemotherapy regimen in combination with 375 mg/m^2 rituximab IV in Cycle 1 (3-4 week-cycles), followed by 1400 mg rituximab SC every 3-4 weeks for 8 cycles (induction period); 1400 mg rituximab SC every 8 weeks for 24 months (Maintenance I period); 1400 mg rituximab SC every 8 weeks until disease progression or end of study, whichever occurs first (Maintenance II period).
    Interventions:
    • Drug: Chemotherapy (Induction Period)
    • Drug: Rituximab
Publications *

*   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 Completed
Actual Enrollment  ICMJE
 (submitted: July 16, 2019)
692
Original Estimated Enrollment  ICMJE
 (submitted: October 26, 2011)
700
Actual Study Completion Date  ICMJE June 2, 2018
Actual Primary Completion Date June 2, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically confirmed Cluster of Differentiation 20-positive (CD20+) follicular NHL Grade 1, 2 or 3a, or other CD20+ indolent NHL (Waldenström's macroglobulinemia or lymphoplasmacytic lymphoma, marginal zone lymphoma) according to World Health Organization (WHO) classification system
  • Participants must have received and must have relapsed or been refractory to, one or more lines of adequate therapy prior to enrollment, including at least one line consisting of immunotherapy and/or chemotherapy and/or radiotherapy
  • Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 2

Exclusion Criteria:

  • Transformation to high-grade lymphoma
  • Aggressive lymphoma (for example, mantle cell lymphoma [MCL])
  • Presence or history of central nervous system (CNS) lymphomatous disease
  • Other malignancy within 5 years prior to enrollment, except for curatively treated carcinoma in situ of the cervix, squamous cell carcinoma of the skin or basal cell skin cancer, or cervical carcinoma Stage 1B or less, breast cancer in situ or localized prostate cancer Stage T1c if treated with curative intent and relapse- and metastasis-free for at least 2 years prior to enrollment
  • Inadequate hematological, hepatic or renal function
  • Known human immunodeficiency virus (HIV) infection
  • Active and/or severe infection (e.g. tuberculosis, sepsis and opportunistic infections, active hepatitis B or C)
  • Pregnant or breastfeeding women
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 Albania,   Argentina,   Austria,   Brazil,   Bulgaria,   Colombia,   Ecuador,   Egypt,   France,   Germany,   Greece,   Hungary,   Italy,   Lithuania,   Norway,   Romania,   Russian Federation,   Slovakia,   Slovenia,   Spain,   Sweden,   Switzerland,   Turkey,   United Kingdom
Removed Location Countries Canada
 
Administrative Information
NCT Number  ICMJE NCT01461928
Other Study ID Numbers  ICMJE MO25455
2010-023407-95 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Hoffmann-La Roche
Study Sponsor  ICMJE Hoffmann-La Roche
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Hoffmann-La Roche
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP