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

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.