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

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT01484093

Collaborator

GlaxoSmithKline (Industry)

Enrollment

Locations

Arm

132

Duration (Months)

19.2

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Mantle Cell Lymphoma	Other: R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR.	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

96 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2011

Anticipated Primary Completion Date :

Nov 1, 2022

Anticipated Study Completion Date :

Nov 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Other: R-CHOP-14R-HIDAC,followed by RIT/HDT/ASCR. 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. Other Names: HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL RESCUE (ASCR)Patients admitted to the hospital for high dose chemotherapy. The anticipated length of stay is 3-4 weeks. 14 days ± 1 day following the administration of the therapeutic dose of Iodine 131 I Tositumomab, patients will be admitted for high-dose chemotherapy. BEAM will be administered

Arm

Intervention/Treatment

Experimental: 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.

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

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.

Other Names:

HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL RESCUE (ASCR)Patients admitted to the hospital for high dose chemotherapy. The anticipated length of

stay is 3-4 weeks. 14 days ± 1 day following the administration of the therapeutic dose of Iodine 131 I

Tositumomab, patients will be admitted for high-dose chemotherapy. BEAM

will be administered

Outcome Measures

Primary Outcome Measures

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

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Memorial Sloan Kettering at Basking Ridge	Basking Ridge	New Jersey	United States	07920
2	Memorial Sloan Kettering Cancer Center @ Suffolk	Commack	New York	United States	11725
3	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065
4	Memorial Sloan Kettering at Mercy Medical Center	Rockville Centre	New York	United States
5	Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center	Sleepy Hollow	New York	United States	10591