Rituximab With or Without Stem Cell Transplant in Treating Patients With Minimal Residual Disease-Negative Mantle Cell Lymphoma in First Complete Remission
Purpose
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.
Condition
- Mantle Cell Lymphoma
Eligibility
- Eligible Ages
- Between 18 Years and 70 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Group I (auto-HCT, rituximab) |
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. |
|
|
Experimental Group II (rituximab) |
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. |
|
More Details
- Status
- Active, not recruiting
- Sponsor
- ECOG-ACRIN Cancer Research Group
Study Contact
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.