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 FISH. 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). Postinduction 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 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.
• 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 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 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-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 seven (7) days of receipt of fresh peripheral blood specimen to the submitting institution and to the ECOG-ACRIN Operations Office.

Eligibility Criteria for Treatment Assignment (STEP 1)

• Patients must have met eligibility criteria for the screening step 0.
• 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.
• 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 150 days prior to registration to Step 1, AND no more than 300 days may have elapsed from the first dose of induction chemotherapy (C1D1) 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.
• Patients must have achieved a radiologic complete or partial remission as defined by the Lugano Criteria.
• In the opinion of the enrolling physician, patients must be felt to be a candidate for autologous stem cell transplantation.
• Patients have an ECOG performance status of 0-2.
• 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 AIDS defining conditions within past 12 months other than historic CD4+ T-cell counts below 200 cells/mm3;
  • Expected long-term survival if lymphoma were not present.
• 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.
• Women 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 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:
  • has not undergone a hysterectomy or bilateral oophorectomy; or
  • 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).
  • Female of child bearing potential? ______ (Yes or No)
  • Date of blood test or urine study: ___________
• 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 and for 12 months post rituximab treatment.