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Rituximab With or Without Stem Cell Transplant in Treating Patients With Minimal Residual Disease-Negative Mantle Cell Lymphoma in First Complete Remission

NCT03267433

Description:

This randomized phase III trial studies rituximab after stem cell transplant and to see how well it works compared with rituximab alone in treating patients with in minimal residual disease-negative mantle cell lymphoma in first complete remission. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving chemotherapy before a stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving rituximab with or without stem cell transplant may work better in treating patients with mantle cell lymphoma.

Related Conditions:
  • Mantle Cell Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Rituximab With or Without Stem Cell Transplant in Treating Patients With Minimal Residual Disease-Negative Mantle Cell Lymphoma in First Complete Remission
  • Official Title: A Randomized Phase III Trial of Consolidation With Autologous Hematopoietic Cell Transplantation Followed by Maintenance Rituximab vs. Maintenance Rituximab Alone for Patients With Mantle Cell Lymphoma in Minimal Residual Disease-Negative First Complete Remission

Clinical Trial IDs

  • ORG STUDY ID: EA4151
  • SECONDARY ID: NCI-2016-01403
  • SECONDARY ID: EA4151
  • SECONDARY ID: EA4151
  • SECONDARY ID: EA4151
  • SECONDARY ID: U10CA180820
  • NCT ID: NCT03267433

Conditions

  • CD20 Positive
  • Mantle Cell Lymphoma

Interventions

DrugSynonymsArms
RituximabGroup I (auto-HCT, rituximab)

Purpose

This randomized phase III trial studies rituximab after stem cell transplant and to see how well it works compared with rituximab alone in treating patients with in minimal residual disease-negative mantle cell lymphoma in first complete remission. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Giving chemotherapy before a stem cell transplant helps kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy. Giving rituximab with or without stem cell transplant may work better in treating patients with mantle cell lymphoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To compare overall survival in mantle cell lymphoma (MCL) patients in minimal residual
      disease (MRD)-negative first remission who undergo autologous hematopoietic stem cell
      transplantation (auto-HCT) followed by maintenance rituximab versus (vs.) maintenance
      rituximab alone (without auto-HCT).

      SECONDARY OBJECTIVES:

      I. To compare progression-free survival in MCL patients in MRD-negative first remission who
      undergo auto-HCT followed by maintenance rituximab vs. maintenance rituximab alone.

      II. To define the overall survival and progression-free survival at 2 and 5 years of
      chemosensitive but MRD-positive (or MRD-indeterminate) patients who undergo auto-HCT followed
      by 2 years of maintenance rituximab.

      III. To describe the rate of complications (serious infection, hospitalization, need for
      intravenous immune globulin) in MCL patients undergoing maintenance rituximab following
      auto-HCT.

      IV. To determine the prognostic impact of MRD status at day 100, in MCL patients who were
      MRD-positive prior to auto-HCT.

      OUTLINE: Patients are randomized to 1 of 2 groups.

      GROUP I: Patients receive standard of care preparative chemotherapy and undergo auto-HCT.
      Beginning 60-120 days after transplant, patients receive rituximab intravenously (IV) once
      every 8 weeks for up to 12 courses in the absence of disease progression or unacceptable
      toxicity.

      GROUP II: Patients receive standard of care induction chemotherapy. Beginning 40-120 days
      after completion of chemotherapy, patients receive rituximab as in Group I.

      After completion of study treatment, patients are followed up every 3 and 6 months for 10
      years.
    

Trial Arms

NameTypeDescriptionInterventions
Group I (auto-HCT, rituximab)ExperimentalPatients receive standard of care preparative chemotherapy and undergo auto-HCT. Beginning 60-120 days after transplant, patients receive rituximab IV once every 8 weeks for up to 12 courses in the absence of disease progression or unacceptable toxicity.
  • Rituximab
Group II (rituximab alone)ExperimentalPatients receive standard of care induction chemotherapy. Beginning 40-120 days after completion of chemotherapy, patients receive rituximab as in Group I.
  • Rituximab

Eligibility Criteria

        Inclusion Criteria:

          -  INCLUSION CRITERIA FOR SCREENING (STEP 0 - PREREGISTRATION)

          -  Patients must have histologically confirmed mantle cell lymphoma, with documented
             cluster of differentiation (CD19) or CD20 expression and cyclin D1 (BCL1) by
             immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ
             hybridization (FISH); the diagnosis must be confirmed by formal hematopathology review
             at the enrolling center, including assessment of Ki-67 proliferation index (=< 30%
             versus > 30% versus ?indeterminate? Ki-67 index)

          -  Patients should be deemed to be potentially eligible and willing candidates for
             auto-HCT by the enrolling physician

          -  Patient may be receiving or have completed induction therapy within 60 days prior to
             preregistration to step 0; no more than 300 days may have passed between the first day
             of induction therapy and preregistration to step 0

               -  For patients who have completed induction therapy, restaging evaluation must show
                  status of partial (PR) or complete response (CR); patients preregistered
                  post-induction with evidence of clinical disease progression are not eligible for
                  preregistration

               -  Up to two regimens of chemotherapy are allowed as long as a continuous response
                  was ongoing throughout therapy

                    -  NOTE: For example, a patient who started treatment with
                       rituximab/bendamustine and was then switched to
                       rituximab(R)-cyclophosphamide, doxorubicin hydrochloride, vincristine
                       sulfate, and prednisone (CHOP) (due to insufficient response or excessive
                       toxicity) would be counted as having received 2 regimens; however, R-CHOP
                       alternating with R-dexamethasone, high-dose cytarabine, and cisplatin (DHAP)
                       as a planned induction regimen would count as one regimen

          -  Patient does not have any documented history of central nervous system (CNS)
             involvement by mantle cell lymphoma; this includes no evidence of parenchymal brain,
             spinal cord, or cerebrospinal fluid involvement; radiculopathy symptoms from nerve
             root compression by lymphoma do not constitute CNS involvement

          -  Patient must have archived formalin-fixed paraffin-embedded (FFPE) tumor tissue
             specimen from the original diagnostic biopsy available for submission to Adaptive
             Biotechnologies for ClonoSEQ ID molecular marker identification of unique clonal
             immunoglobulin deoxyribonucleic acid (DNA) sequence

               -  NOTE: Patients for whom the molecular marker is identified will have peripheral
                  blood collected after completion of induction (patient?s disease status is PR or
                  CR) and submitted to Adaptive Biotechnologies for minimal residual disease (MRD)
                  assessment

          -  INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1)

          -  Patients must have met eligibility criteria for the screening step

          -  Institution has received results from Adaptive Biotechnologies as defined by one of
             the following criteria:

               -  Patients are ?MRD Indeterminate?: ClonoSEQ ID molecular marker assessment did not
                  identify any unique clonal immunoglobulin DNA sequence OR

               -  ClonoSEQ ID molecular marker assessment identified unique clonal immunoglobulin
                  DNA sequence and MRD assessment is completed

          -  Patients must have completed induction therapy within 120 days prior to
             preregistration to step 0, AND no more than 300 days may have elapsed from the first
             dose of induction chemotherapy (cycle 1 [C1] day 1 [D1]) given, until the last day of
             induction chemotherapy administered; for those assigned to Arms A, C, or D, the date
             of transplant (?day 0?) must not be greater than 365 days after the first dose of
             induction chemotherapy (C1D1) given

               -  Patient must have received at least four (4) cycles of induction therapy

               -  Up to two regimens of chemotherapy are allowed as long as a continuous response
                  was ongoing throughout therapy

                    -  NOTE: For example, a patient who started treatment with
                       rituximab/bendamustine and was then switched to R-CHOP (due to insufficient
                       response or excessive toxicity) would be counted as having received 2
                       regimens; however, R-CHOP alternating with R-DHAP as a planned induction
                       regimen would count as one regimen

          -  Patients must have achieved a radiologic complete or partial remission as defined by
             the Lugano criteria

          -  Patients must meet institutional eligibility requirements for stem cell transplant,
             including cardiac, renal, liver, and pulmonary requirements

          -  Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

          -  Human immunodeficiency virus (HIV) positive patients are not excluded, but to enroll,
             must meet all of the below criteria:

               -  HIV is sensitive to antiretroviral therapy

               -  Must be willing to take effective antiretroviral therapy if indicated

               -  CD4 count at screening >= 300 cells/mm^3

               -  No history of acquired immune deficiency syndrome (AIDS)-defining conditions

          -  Patient must be disease-free >= 3 years of prior malignancies with the exception of
             adequately treated non-melanoma skin cancer, adequately treated in situ carcinoma, low
             grade prostate carcinoma (Gleason grade =< 6) managed with observation that has been
             stable for at least 6 months

          -  Women must not be pregnant or breast-feeding

               -  All females of childbearing potential must have a blood test or urine study
                  within 2 weeks prior to registration to rule out pregnancy

               -  A female of childbearing potential is any woman, regardless of sexual orientation
                  or whether they have undergone tubal ligation, who meets the following criteria:
                  1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been
                  naturally postmenopausal for at least 24 consecutive months (i.e., has had menses
                  at any time in the preceding 24 consecutive months)

          -  Women of childbearing potential and sexually active males must be strongly advised to
             use an accepted and effective method of contraception or to abstain from sexual
             intercourse for the duration of their participation in the study
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS) in MCL patients in MRD-negative first remission who undergo auto-HCT followed by rituximab vs. maintenance rituximab alone
Time Frame:Time between randomization and death from any cause, assessed up to 10 years
Safety Issue:
Description:The Kaplan-Meier method will be used to estimate OS, including medians and confidence intervals. Comparison of OS between treatment arms will be conducted using a one-sided log-rank test stratified with mantle cell lymphoma International Prognostic Index (MIPI)-c score and induction regimen.

Secondary Outcome Measures

Measure:Incidence of adverse events evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 10 years
Safety Issue:
Description:The primary safety analysis will be based on the toxicity population, and the analysis will be performed by treatment received.
Measure:MRD status in MCL patients who were MRD-positive prior to auto-HCT
Time Frame:At 100 days
Safety Issue:
Description:Will be reported together with confidence intervals.
Measure:OS in MRD-positive patients (or patients in PR) who undergo auto-HCT followed by rituximab
Time Frame:Time between randomization and death from any cause, assessed up to 10 years
Safety Issue:
Description:Will be estimated by the method of Kaplan and Meier.
Measure:PFS in MRD-positive patients (or patients in PR) who undergo auto-HCT followed by rituximab
Time Frame:From randomization to the earliest of documented disease progression or death without progression, assessed up to 10 years
Safety Issue:
Description:Will be estimated by the method of Kaplan and Meier.
Measure:Progression-free survival (PFS) in MCL patients in MRD-negative first remission who undergo auto-HCT followed by rituximab vs rituximab alone
Time Frame:From randomization to the earliest of documented disease progression or death without progression, assessed up to 10 years
Safety Issue:
Description:The method of Kaplan and Meier will be used to estimate PFS, and stratified log-rank test will be used to compare PFS between two arms.
Measure:Rate of complications in MCL patients undergoing maintenance rituximab
Time Frame:Up to 10 years
Safety Issue:
Description:

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:ECOG-ACRIN Cancer Research Group

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