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.
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 autoHCT).
Secondary Objectives:
1.To compare progression-free survival in MCL patients in MRD negative CR who undergo auto-HCT followed by maintenance rituximab vs. maintenance rituximab alone.
2. 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.
3. 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.
4. 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.
5. 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.
6. To describe the rate of complications (serious infection, hospitalization, need for intravenous immune globulin) in MCL patients undergoing maintenance rituximab following auto-HCT.
7. 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.
- Rutgers Cancer Institute of New Jersey
- Principal Investigator
- Matthew Matasar
- Principal Investigator
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
Please note that we have obtained the inclusion and exclusion criteria information from the National Institutes of Health’s clinical trials web site ClinicalTrials.gov. The listed criteria may not necessarily reflect recent amendments to the protocol and the current criteria.
For further information about clinical trials, please contact us at 732-235-7356.