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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03267433
Recruitment Status : Recruiting
First Posted : August 30, 2017
Last Update Posted : May 12, 2023
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Eastern Cooperative Oncology Group ( ECOG-ACRIN Cancer Research Group )

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
CD20 Positive Mantle Cell Lymphoma Procedure: Autologous Hematopoietic Stem Cell Transplantation Other: Laboratory Biomarker Analysis Biological: Rituximab Phase 3

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 18 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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 689 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : August 29, 2017
Estimated Primary Completion Date : January 31, 2027
Estimated Study Completion Date : January 31, 2032

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Group I (auto-HCT, rituximab)
Patients 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.
 Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo HCT
Other Names:
  • Autologous Hematopoietic Cell Transplantation
  • autologous stem cell transplantation

Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Rituximab
Given IV
Experimental: Group II (rituximab alone)
Patients receive standard of care induction chemotherapy. Beginning 40-120 days after completion of chemotherapy, patients receive rituximab as in Group I.
 Other: Laboratory Biomarker Analysis
Correlative studies

Biological: Rituximab
Given IV


Outcome Measures
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Primary Outcome Measures :
  1. 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 ]
    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 :
  1. 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 ]
    The primary safety analysis will be based on the toxicity population, and the analysis will be performed by treatment received.

  2. MRD status in MCL patients who were MRD-positive prior to auto-HCT [ Time Frame: At 100 days ]
    Will be reported together with confidence intervals.

  3. 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 ]
    Will be estimated by the method of Kaplan and Meier.

  4. 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 ]
    Will be estimated by the method of Kaplan and Meier.

  5. 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 ]
    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.

  6. Rate of complications in MCL patients undergoing maintenance rituximab [ Time Frame: Up to 10 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • INCLUSION CRITERIA FOR SCREENING (STEP 0 - PREREGISTRATION)
  • Patients must have histologically confirmed mantle cell lymphoma, with cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or FISH. If patient has cyclin D1 negative mantle cell lymphoma with classical morphology and an expression profile (including SOX11+) that is otherwise indistinguishable from mantle cell lymphoma, communication with investigator is required for consideration of enrollment. The proliferation rate, using Ki-67 or MIB-1, should also be determined, but is not required until Step 1 registration. Patients may register to Step 0 without a documented 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
Contacts and Locations
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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): NCT03267433


Locations
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Sponsors and Collaborators
ECOG-ACRIN Cancer Research Group
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Timothy Fenske ECOG-ACRIN Cancer Research Group
More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: ECOG-ACRIN Cancer Research Group
ClinicalTrials.gov Identifier: NCT03267433    
Other Study ID Numbers: EA4151
NCI-2016-01403 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
EA4151
EA4151 ( Other Identifier: ECOG-ACRIN Cancer Research Group )
EA4151 ( Other Identifier: CTEP )
U10CA180820 ( U.S. NIH Grant/Contract )
First Posted: August 30, 2017    Key Record Dates
Last Update Posted: May 12, 2023
Last Verified: May 2023

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Mantle-Cell
Neoplasm, Residual
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
 Lymphoma, Non-Hodgkin
Neoplastic Processes
Pathologic Processes
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents