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

Recruitment & Eligibility

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.

Study & Design

Arm && Interventions

Group	Intervention	Description
R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.	R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.	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.

Primary Outcome Measures

Name	Time	Method
maximum tolerated dose (MTD)	1 year	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
3 year Event Free Survival (EFS)	3 years	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

Secondary Outcome Measures

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

Trial Locations

Locations (5)

Memorial Sloan Kettering at Basking Ridge

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Basking Ridge, New Jersey, United States

Memorial Sloan Kettering Cancer Center

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New York, New York, United States

Memorial Sloan Kettering Cancer Center @ Suffolk

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Commack, New York, United States

Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center

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Sleepy Hollow, New York, United States

Memorial Sloan Kettering at Mercy Medical Center

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Rockville Centre, New York, United States

Recruitment & Eligibility