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NCT03267433 · CITED IN SOURCE DOCUMENTS

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

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE3
Status at capture
ACTIVE NOT RECRUITING
Registry last update
2026-07-17

This 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. Immunotherapy with rituximab, may induce changes in body's immune system and may interfere with the ability of tumor 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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

No posted result sections were captured. Registered plans do not establish that a treatment works.

Who could take part
eligibility Criteria
Inclusion Criteria: * INCLUSION CRITERIA FOR SCREENING (STEP 0 - PREREGISTRATION) * Age \>= 18 and =\< 70 years * Patients must have histologically confirmed mantle cell lymphoma, with cyclin D1 by immunohistochemical stains and/or t(11;14) by cytogenetics or fluorescence in situ hybridization (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 * In the opinion of the enrolling physician, patients must be felt to be a candidate for autologous stem cell transplantation * Patient may be about to begin, be receiving or have completed induction therapy within 120 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 and have been restaged, restaging evaluation must show status of partial (PR) or complete response (CR); post-induction patients with evidence of clinical disease progression are not eligible for preregistration * Up to two regimens of therapy (conventional chemotherapy, antibody therapy, or an oral regimen) are allowed as long as a continuous response was ongoing throughout therapy; overall, a partial response needs to have been achieved (using studies at the time of diagnosis as the baseline) * 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: If adequate tumor tissue is not available, peripheral blood collected prior to start of treatment with high disease burden (\> 5%) is acceptable for molecular marker identification (ID) testing * Adaptive Biotechnologies will forward results within fourteen (14) days of receipt of any stored (e.g. frozen or FFPE) tumor tissue specimen to the submitting institution and to the ECOG-American College of Radiology Imaging Network (ACRIN) Operations Office * 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 * Adaptive Biotechnologies will forward results within ten to fourteen (10-14) days of receipt of fresh peripheral blood specimen to the submitting institution and to the ECOG-ACRIN Operations Office * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): Patients must have met eligibility criteria for the screening step 0 * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): The proliferation rate, using Ki-67 or MIB-1 immunohistochemistry (=\< 30% versus \> 30% versus "indeterminate" Ki-67 index), must be documented for a baseline tumor biopsy specimen * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): 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 * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): Patients must have completed induction therapy within 150 days prior to registration to step 1, 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 therapy (conventional chemotherapy, antibody therapy, or an oral regimen) 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 * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): Patients must have achieved a radiologic complete or partial remission as defined by the Lugano criteria * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): In the opinion of the enrolling physician, patients must be felt to be a candidate for autologous stem cell transplantation * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): Patients have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): 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 that has minimal overlapping toxicity and pharmacokinetic interactions with protocol therapy * No history of HIV-related opportunistic disease or acquired immune deficiency syndrome (AIDS)-defining conditions within past 12 months other than historic CD4+ T-cell counts below 200 cells/mm\^3 * Expected long-term survival if lymphoma were not present * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): 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, melanoma in situ post wide local excision or Mohs surgery, low grade prostate carcinoma (Gleason grade =\< 6) managed with observation that has been stable for at least 6 months * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): Patient must not be pregnant or breast-feeding due to the potential for congenital abnormalities and of harm to nursing infants due to the treatment regimens used * All patients of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy * A patient of childbearing potential is anyone, 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) * INCLUSION CRITERIA FOR TREATMENT ASSIGNMENT (STEP 1): Patient 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 and for 12 months post rituximab treatment
healthy Volunteers
false
maximum Age
70 Years
minimum Age
18 Years
sex
ALL
std Ages
  1. ADULT
  2. OLDER_ADULT
Treatment arms and interventions
arm Groups
  1. description
    Patients receive standard of care preparative chemotherapy and undergo auto-HCT. Beginning 100-140 days after transplant, patients receive rituximab IV or rituximab and hyaluronidase human SC or any approved rituximab biosimilar at the approved dose once every 8 weeks for up to 18 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PET, CT or PET/CT throughout the study. Patients may undergo blood sample collection during screening and on study. Patients also may undergo bone marrow biopsy and aspirate during screening.
    intervention Names
    1. Procedure: Autologous Hematopoietic Stem Cell Transplantation
    2. Procedure: Biospecimen Collection
    3. Procedure: Bone Marrow Aspirate
    4. Procedure: Bone Marrow Biopsy
    5. Procedure: Computed Tomography
    6. Procedure: Positron Emission Tomography
    7. Biological: Rituximab
    8. Biological: Rituximab and Hyaluronidase Human
    label
    Group I (auto-HCT, rituximab)
    type
    EXPERIMENTAL
  2. description
    Patients receive standard of care induction chemotherapy. Beginning 40-180 days after completion of chemotherapy, patients receive rituximab or rituximab and hyaluronidase human or any approved rituximab biosimilar at the approved dose, as in Group I. Patients undergo PET, CT or PET/CT throughout the study. Patients may undergo blood sample collection during screening and on study. Patients also may undergo bone marrow biopsy and aspirate during screening.
    intervention Names
    1. Procedure: Biospecimen Collection
    2. Procedure: Bone Marrow Aspirate
    3. Procedure: Bone Marrow Biopsy
    4. Procedure: Computed Tomography
    5. Procedure: Positron Emission Tomography
    6. Biological: Rituximab
    7. Biological: Rituximab and Hyaluronidase Human
    label
    Group II (rituximab)
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Group I (auto-HCT, rituximab)
    description
    Undergo HCT
    name
    Autologous Hematopoietic Stem Cell Transplantation
    other Names
    1. AHSCT
    2. Autologous
    3. Autologous Hematopoietic Cell Transplantation
    4. Autologous Stem Cell Transplant
    5. Autologous Stem Cell Transplantation
    6. Stem Cell Transplantation, Autologous
    type
    PROCEDURE
  2. arm Group Labels
    1. Group I (auto-HCT, rituximab)
    2. Group II (rituximab)
    description
    Undergo blood sample collection
    name
    Biospecimen Collection
    other Names
    1. Biological Sample Collection
    2. Biospecimen Collected
    3. Specimen Collection
    type
    PROCEDURE
  3. arm Group Labels
    1. Group I (auto-HCT, rituximab)
    2. Group II (rituximab)
    description
    Undergo bone marrow biopsy and aspirate
    name
    Bone Marrow Aspirate
    other Names
    1. BONE MARROW, LIQUID
    2. Human Bone Marrow Aspirate
    type
    PROCEDURE
  4. arm Group Labels
    1. Group I (auto-HCT, rituximab)
    2. Group II (rituximab)
    description
    Undergo bone marrow biopsy and aspirate
    name
    Bone Marrow Biopsy
    other Names
    1. Biopsy of Bone Marrow
    2. Biopsy, Bone Marrow
    type
    PROCEDURE
  5. arm Group Labels
    1. Group I (auto-HCT, rituximab)
    2. Group II (rituximab)
    description
    Undergo CT or PET/CT
    name
    Computed Tomography
    other Names
    1. CAT
    2. CAT Scan
    3. Computed Axial Tomography
    4. Computerized Axial Tomography
    5. Computerized axial tomography (procedure)
    6. Computerized Tomography
    7. Computerized Tomography (CT) scan
    8. CT
    9. CT Scan
    10. tomography
    type
    PROCEDURE
  6. arm Group Labels
    1. Group I (auto-HCT, rituximab)
    2. Group II (rituximab)
    description
    Undergo PET or PET/CT
    name
    Positron Emission Tomography
    other Names
    1. Medical Imaging, Positron Emission Tomography
    2. PET
    3. PET Scan
    4. Positron emission tomography (procedure)
    5. Positron Emission Tomography Scan
    6. Positron-Emission Tomography
    7. proton magnetic resonance spectroscopic imaging
    8. PT
    type
    PROCEDURE
  7. arm Group Labels
    1. Group I (auto-HCT, rituximab)
    2. Group II (rituximab)
    description
    Given IV
    name
    Rituximab
    other Names
    1. ABP 798
    2. BI 695500
    3. BI-695500
    4. BI695500
    5. Blitzima
    6. C2B8 Monoclonal Antibody
    7. Chimeric Anti-CD20 Antibody
    8. CT-P10
    9. IDEC 102
    10. IDEC-102
    11. IDEC-C2B8
    12. IDEC-C2B8 Monoclonal Antibody
    type
    BIOLOGICAL
  8. arm Group Labels
    1. Group I (auto-HCT, rituximab)
    2. Group II (rituximab)
    description
    Given SC
    name
    Rituximab and Hyaluronidase Human
    other Names
    1. Rituxan Hycela
    2. Rituximab Plus Hyaluronidase
    3. Rituximab/Hyaluronidase
    4. Rituximab/Hyaluronidase Human
    type
    BIOLOGICAL
Study design
allocation
RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
689
type
ESTIMATED
Registered outcome plans (not posted results)
primary Outcomes
  1. 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.
    measure
    Overall survival (OS) in mantle cell lymphoma (MCL) patients in minimal residual disease (MRD)-negative complete remission (CR) who undergo auto-hematopoietic stem cell transplant (HCT) followed by rituximab versus (vs.) maintenance rituximab alone
    time Frame
    Time between randomization and death from any cause, assessed up to 10 years
secondary Outcomes
  1. 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
    Progression-free survival (PFS) in MCL patients in MRD-negative CR 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
  2. description
    Will be estimated by the method of Kaplan and Meier.
    measure
    PFS in MRD-negative PR patients, MRD-positive CR patients, MRD-positive PR patients, and MRD-indeterminate patients 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
  3. description
    Will be estimated by the method of Kaplan and Meier.
    measure
    OS in MRD-negative PR patients, MRD-positive CR patients, MRD-positive PR patients, and MRD-indeterminate patients who undergo auto-HCT followed by rituximab
    time Frame
    Time between randomization and death from any cause, assessed up to 10 years
  4. measure
    Rate of complications in MCL patients undergoing maintenance rituximab
    time Frame
    Up to 10 years
  5. description
    Conversion rate will be reported together with confidence intervals.
    measure
    MRD status in MCL patients who were MRD-positive prior to auto-HCT
    time Frame
    At 100 days after HCT
  6. description
    Will be evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0. The primary safety analysis will be based on the toxicity population, and the analysis will be performed by treatment received.
    measure
    Incidence of adverse events
    time Frame
    Up to 10 years
Full study description
brief Summary
This 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. Immunotherapy with rituximab, may induce changes in body's immune system and may interfere with the ability of tumor 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 OBJECTIVE: I. To compare overall survival in mantle cell lymphoma (MCL) patients in minimal residual disease (MRD)-negative first complete remission (CR) 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 CR 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 CR patients who undergo auto-HCT followed by 3 years of maintenance rituximab. III. To define the overall survival and progression-free survival at 2 and 5 years of chemosensitive but MRD-positive partial response (PR) patients who undergo auto-HCT followed by 3 years of maintenance rituximab. IV. To define the overall survival and progression-free survival at 2 and 5 years of MRD-negative PR patients who undergo auto-HCT followed by 3 years of maintenance rituximab. V. To define the overall survival and progression-free survival at 2 and 5 years of MRD-indeterminate patients who undergo auto-HCT followed by 3 years of maintenance rituximab. VI. To describe the rate of complications (serious infection, hospitalization, need for intravenous immune globulin) in MCL patients undergoing maintenance rituximab following auto-HCT. VII. To determine the prognostic impact of MRD status at day 100, in MCL patients who were MRD-positive (including MRD-positive CR and MRD-positive PR) prior to auto-HCT. EXPLORATORY TOBACCO USE OBJECTIVES: I. To determine the effects of tobacco, operationalized as combustible tobacco (1a), other forms of tobacco (1b), and environmental tobacco exposure (ETS) (1c) on provider-reported cancer-treatment toxicity (adverse events (both clinical and hematologic) and dose modifications). II. To determine the effects of tobacco on patient-reported physical symptoms and psychological symptoms. III. To examine quitting behaviors and behavioral counseling/support and cessation medication utilization. IV. To explore the effect of tobacco use and exposure on treatment duration, relative dose intensity, and therapeutic benefit. OUTLINE: Patients are randomized to 1 of 2 groups. GROUP I: Patients receive standard of care preparative chemotherapy and undergo auto-HCT. Beginning 100-140 days after transplant, patients receive rituximab intravenously (IV) or rituximab and hyaluronidase human subcutaneously (SC) or any approved rituximab biosimilar at the approved dose once every 8 weeks for up to 18 cycles in the absence of disease progression or unacceptable toxicity. GROUP II: Patients receive standard of care induction chemotherapy. Beginning 40-180 days after completion of chemotherapy, patients receive rituximab or rituximab and hyaluronidase human or any approved rituximab biosimilar at the approved dose, as in Group I. Patients undergo positron emission tomography (PET), computed tomography (CT) or PET/CT throughout the study. Patients may undergo blood sample collection during screening and on study. Patients also may undergo bone marrow biopsy and aspirate during screening. After completion of study treatment, patients are followed up every 3 and 6 months for 10 years.
Source references
references
  1. citation
    Kumar A. What is the role of up-front autologous stem cell transplantation in mantle cell lymphoma? Hematology Am Soc Hematol Educ Program. 2022 Dec 9;2022(1):155-162. doi: 10.1182/hematology.2022000333.
    pmid
    36485104
    type
    DERIVED
  2. citation
    Thiruvengadam SK, Hunter B, Varnavski A, Fakhri B, Kaplan L, Ai WZ, Pampaloni M, Huang CY, Martin T 3rd, Damon L, Andreadis CB. Ofatumumab, Etoposide, and Cytarabine Intensive Mobilization Regimen in Patients with High-risk Relapsed/Refractory Diffuse Large B-Cell Lymphoma Undergoing Autologous Stem Cell Transplantation. Clin Lymphoma Myeloma Leuk. 2021 Apr;21(4):246-256.e2. doi: 10.1016/j.clml.2020.11.005. Epub 2020 Nov 11.
    pmid
    33288485
    type
    DERIVED
Source notices and limitations
    Discovery and provenance
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        outcomes by 5% for OS. Autologous SCT did not add efficacy to the ibrutinib-containing regimens but did add toxicity.</p></li><li>The <a href="/clinicaltrials/NCT03267433">ECOG 4151</a> trial (NCT03267433), published in abstract form, included 650 patients younger than 71 years with previously untreated MCL who were eligible fo
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        SCT did not add efficacy to the ibrutinib-containing regimens but did add toxicity.</p></li><li>The <a href="/clinicaltrials/NCT03267433">ECOG 4151</a> trial (NCT03267433), published in abstract form, included 650 patients younger than 71 years with previously untreated MCL who were eligible for autologous SCT. The trial allowe
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      source update dates
      1. context
        Updated: May 12, 2025
        datetime
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        May 12, 2025

    Preserved source evidence · Not medical advice