Sequential Chemo-Radioimmunotherapy Followed by Autologous Transplantation for Patients With Untreated Advanced Stage Mantle Cell Lymphoma

Study Overview
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Brief Summary
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Mantle cell lymphoma (MCL) is a rare and aggressive type of lymphoma, with only about 3,000 cases diagnosed per year. MCL is considered a difficult cancer to treat. This study is being done to better understand how to treat MCL.

Official Title
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Sequential Chemo-Radioimmunotherapy Followed by Autologous Transplantation for Patients With Untreated Advanced Stage Mantle Cell Lymphoma: A Phase I/II Trial

Conditions
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Mantle Cell Lymphoma

Intervention / Treatment
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* Other: R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Previously untreated advanced stage mantle cell lymphoma (Clinical stage 2 with abdominal involvement, stage 3 and stage 4). Histologic diagnosis confirmed by MSKCC pathologist as mantle cell lymphoma with Cyclin D1, or D2 and/or, D3 staining performed. Presence of measurable disease as determined by FDG-PET, CT, endoscopy, colonoscopy, or bone marrow biopsy. Ages 18-70. Transplant eligibility as confirmed by the Disease Management Team. KPS ≥ 70%. Adequate organ function: WBC ANC ≥ 1000 cells/mcL and platelet count ≥ 100,000 cells/mcL unless felt to be secondary to underlying mantle cell lymphoma at which any count is permissible. Adequate renal function as determined by Cr < or = to 1.5 mg/dL or 24 hr creatinine clearance ≥ 50 ml/hr Adequate hepatic function as determined by total bilirubin < or = to 1.5x ULN (unless known Gilbert syndrome) and AST < or = to 5.0x ULN. Cardiac ejection fraction greater than or equal to 50% as determined by echocardiogram or MUGA. For patients ≥ age 60, a stress echocardiogram will be required, with same requirements as above. DLCO greater than or equal to 50% as determined by pulmonary function tests performed prior to initiation of treatment. Patients with positive Hepatitis B serologies will be treated per institutional guidelines. Exclusion Criteria: Prior treatment for mantle cell lymphoma, including more than 7 days of steroids, immunotherapy, radioimmunotherapy, or chemotherapy. This does not include patients who have initiated R-CHOP at an outside institution within 2 weeks of enrollment. Patients using > or = to 10mg/day of steroids for any chronic medical condition Pregnant or breast-feeding. Note: Pre-menopausal patients must have a negative, serum HCG within 14 days of enrollment,. HIV positive or Hepatitis C antibody positive.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.<br>This is a phase I/phase II multi-institution trial. The phase I part of the trial will determine the MTD of cytarabine. The phase II part of the trial will examine the efficacy of the proposed regimen by evaluating the 3-year event-free survival (EFS) in patients with untreated mantle cell lymphoma. All patients in the study in both phases will undergo induction and consolidation with R-CHOP 14R-HIDAC, followed by RIT/HDT/ASCR. | Other: R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.<br>* INDUCTION: R-CHOP-14 CHEMOTHERAPY: 4 cycles every 2 weeks ± 1 day All patients in the study in both phases will undergo induction and consolidation with R-CHOP 14R-HIDAC, followed by RIT/HDT/ASCR. Patients will undergo restaging scans 12 to 14 days following completion of R-CHOP 14, with CT, and FDG-PET. Patients demonstrating at least a PR may proceed to consolidation with R-HIDAC. CONSOLIDATION: R- HIDAC CHEMOTHERAPY: 2 cycles every 3 weeks ± 2 days After R-HIDAC, restaging will occur 17-21 days post cycle 2 with CT scan (or FDG-PET, if this was positive following R-CHOP-14). Radioimmunotherapy Dosimetric dose is given approximately 4-5 weeks after completing cycle 2 of R-HIDAC. This is to be preferred 1 week post restaging scans 17-21 days post cycle 2 of RHIDAC, and up to 2 weeks post-scans will be acceptable only if required by 131 I Tositumomab availability.<br>* Other names: will be administered;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| maximum tolerated dose (MTD) | of HIDAC. For this study the MTD will be the dose at which no more than one grade 3 CNS toxic event (defined by CTCAE 4.0 as severe neurologic symptoms limiting self care ADLs') up to two weeks following HIDAC occurs among a 6 patient cohort. Phase I | 1 year | 
| 3 year Event Free Survival (EFS) | from 67% (historical control) to 80 % in all patients. The EFS interval starts at enrollment date, and an event is defined as death from any cause or progression of disease. Patients who have completed the ASCT but elect to be removed from the study or lost to follow-up by the end of the third year will be counted as events as well. Phase II | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-year Event Free Survival (EFS) | in subsets of patients with Ki-67 ≥ 30% | 3 years | 
| rates of complete remission (CR) | as defined by CT, FDG-PET and histology | 1 year | 
| Determine 3 year overall survival (OS). | Defined as last known follow up or date of death - date of diagnosis. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CYCLOPHOSPHAMIDE (CYTOXAN), CYTARABINE (ARA-C), DOXORUBICIN/ADRIAMYCIN, PREDNISONE, RITUXIMAB, TOSITUMOMAB (BEXXAR), Iodine, VINCRISTIN, Lymphoma, Chemo-Radioimmunotherapy, Autologous Transplantation, Untreated, 11-095