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

Cancer Categories

Hematologic (Blood Cancers)

Karmanos Trial ID

EA4151/BMTCTN1601

NCT ID

NCT03267433

Age Group

Adult

Scope

National

Phase

Phase III

Principal Investigator

Joseph
Uberti, M.D., Ph.D.
Oncology - Hematology, Oncology - Medical View Profile

Objective:

Primary Objective:

To compare overall survival in MCL patients in MRD-negative first complete remission (CR) who undergo auto-HCT followed by maintenance rituximab vs. maintenance rituximab alone (without auto- HCT).

Secondary Objectives:

To compare progression-free survival in MCL patients in MRDnegative CR who undergo auto-HCT followed by maintenance rituximab vs. maintenance rituximab alone.
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.
To define the overall survival and progression-free survival at 2 and 5 years of chemosensitive but MRD-positive PR patients who undergo auto-HCT followed by 3 years of maintenance rituximab.
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.
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.
To describe the rate of complications (serious infection, hospitalization, need for intravenous immune globulin) in MCL patients undergoing maintenance rituximab following auto-HCT.
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.

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Eligibility

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)

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