Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma

Sponsor

Alliance for Clinical Trials in Oncology (Other)

Overall Status

Completed

CT.gov ID

NCT00006747

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

0.1

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by chemotherapy used to kill cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by donor peripheral stem cell transplantation in treating patients who have mantle cell lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Graft Versus Host Disease Lymphoma	Drug: carmustine Drug: melphalan Drug: etoposide Drug: cytarabine Drug: tacrolimus Drug: methotrexate Drug: sargramostim Procedure: transplant	Phase 2

Detailed Description

OBJECTIVES:

Determine the long term disease-free survival of patients with mantle cell lymphoma treated with etoposide, carmustine, melphalan, and cytarabine followed by allogeneic peripheral blood stem cell transplantation.
Determine the incidence of molecular remissions in these patients treated with this regimen.
Correlate the persistence of minimal residual disease with clinical outcome in these patients treated with this regimen.
Determine the effect of donor lymphocytes in patients with progressive disease after treatment with this regimen.

OUTLINE: This is a multicenter study.

Patients receive carmustine IV over 2 hours on day -6; etoposide IV over 3 hours and cytarabine IV over 1 hour every 12 hours on days -5 to -2 for a total of 8 doses; and melphalan IV over 20-30 minutes on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplantation on day 0. Patients also receive tacrolimus IV continuously over 24 hours beginning on day -2 and then orally twice daily until day 120 and methotrexate IV over 30 minutes on days 1, 3, and 6 as graft-versus-host disease (GVHD) prophylaxis. Patients receive sargramostim (GM-CSF) IV or subcutaneously daily beginning on day 7 and continuing until blood counts recover.

Patients with no active GVHD who have persistent disease on day 150 or progressive disease at any time after PBSC transplantation receive donor lymphocytes IV over 2 hours. Patients may receive additional donor lymphocytes at least 8 weeks later if disease persists.

Patients are followed at 6 and 12 months posttransplantation and then annually for 4 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

4 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Allogeneic Stem Cell Transplantation for Mantle Cell Lymphoma

Study Start Date :

Nov 1, 2000

Actual Primary Completion Date :

Feb 1, 2003

Actual Study Completion Date :

Feb 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: chemotherapy + stem cell transplantation Patients receive carmustine, etoposide, cytarabine and melphalan on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplantation on day 0. Patients also receive tacrolimus on day -2 and then orally twice daily until day 120 and methotrexate on days 1, 3, and 6 as graft-versus-host disease (GVHD) prophylaxis. Patients receive sargramostim daily beginning on day 7 and continuing until blood counts recover. Patients with no active GVHD who have persistent disease on day 150 or progressive disease at any time after PBSC transplantation receive donor lymphocytes IV over 2 hours. Patients may receive additional donor lymphocytes at least 8 weeks later if disease persists. Patients are followed at 6 and 12 months post-transplantation and then annually for 4 years.	Drug: carmustine IV Drug: melphalan IV Drug: etoposide IV Drug: cytarabine IV Drug: tacrolimus IV Drug: methotrexate IV Drug: sargramostim IV Procedure: transplant

Arm

Intervention/Treatment

Experimental: chemotherapy + stem cell transplantation

Patients receive carmustine, etoposide, cytarabine and melphalan on day -1. Patients undergo allogeneic peripheral blood stem cell (PBSC) transplantation on day 0. Patients also receive tacrolimus on day -2 and then orally twice daily until day 120 and methotrexate on days 1, 3, and 6 as graft-versus-host disease (GVHD) prophylaxis. Patients receive sargramostim daily beginning on day 7 and continuing until blood counts recover. Patients with no active GVHD who have persistent disease on day 150 or progressive disease at any time after PBSC transplantation receive donor lymphocytes IV over 2 hours. Patients may receive additional donor lymphocytes at least 8 weeks later if disease persists. Patients are followed at 6 and 12 months post-transplantation and then annually for 4 years.

Drug: carmustine

Drug: melphalan

Drug: etoposide

Drug: cytarabine

Drug: tacrolimus

Drug: methotrexate

Drug: sargramostim

Procedure: transplant

Outcome Measures

Primary Outcome Measures

disease free survival [up to 5 years post-transplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 59 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Documentation of Disease
Histologically documented mantle cell lymphoma of any stage (needle or core biopsy is not acceptable as the sole means of diagnosis) with at least one of the following confirmatory tests indicative of diagnosis:

Immunophenotype with expression of CD5 and CD19 and absence of CD23
Cytogenetic analysis with presence of t(11;14)
Overexpression of cyclin D1
Rearrangement of BCL1 gene

Rebiopsy of a node at relapse is recommended but not required.
Bone marrow biopsy required for pretreatment evaluation. Bilateral biopsies are not required.
Identification of HLA-Matched sibling donor - The sibling donor must meet eligibility criteria outlined in section 5.0
Prior Therapy
Patients who have failed initial therapy are eligible (without any of the poor prognostic characteristics listed in the protocol). Failure to initial treatment is defined as one of the following:

Failure to achieve clinical complete remission after treatment with an anthracycline-containing regimen
Disease recurrence after initial treatment (with an anthracycline-containing regimen)

Patients in first remission must have one of the following poor prognostic characteristics:

International Prognostic Index (IPI) score > 1. IPI risk factors include the following: age > 60 (not eligible for this protocol); performance status > 1; LDH > normal; presence of > 1 extranodal sites; and stage III/IV disease
Blastic variant of mantle cell lymphoma (regardless of IPI score)
Complex karyotypes (i.e., cytogenetic abnormalities different from or in addition to t(11;14) (regardless of IPI score)
Proliferative index > 10% (regardless of IPI score)
Presence of p53 mutations

Patients who have received more than two chemotherapy regimens are ineligible. Patients who have undergone a prior bone marrow transplant are not eligible.
Age < 60 years
No active CNS lymphoma
DLCO ≥ 40% and no symptomatic pulmonary disease
No HIV infection
Non-pregnant and non-nursing. Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.
Initial required laboratory values

bilirubin < 2 mg/dl
AST ≤ 3 x upper limit of normal (ULN)
ALT ≤ 3 x ULN
serum creatinine < 2 mg/dl
u-HCG or serum HCG negative (if patient of childbearing potential)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Veterans Affairs Medical Center - Birmingham	Birmingham	Alabama	United States	35233-1996
2	University of California San Diego Cancer Center	La Jolla	California	United States	92093-0658
3	Veterans Affairs Medical Center - San Francisco	San Francisco	California	United States	94121
4	UCSF Cancer Center and Cancer Research Institute	San Francisco	California	United States	94143-0128
5	CCOP - Christiana Care Health Services	Wilmington	Delaware	United States	19899
6	Lombardi Cancer Center	Washington	District of Columbia	United States	20007
7	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5000
8	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
9	University of Illinois at Chicago	Chicago	Illinois	United States	60612
10	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois	United States	60612
11	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
12	Holden Comprehensive Cancer Center	Iowa City	Iowa	United States	52242-1009
13	Veterans Affairs Medical Center - Togus	Togus	Maine	United States	04330
14	Marlene and Stewart Greenebaum Cancer Center, University of Maryland	Baltimore	Maryland	United States	21201
15	Dana-Farber Cancer Institute	Boston	Massachusetts	United States	02115
16	University of Massachusetts Memorial Medical Center - University Campus	Worcester	Massachusetts	United States	01655
17	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55417
18	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
19	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri	United States	65201
20	Ellis Fischel Cancer Center - Columbia	Columbia	Missouri	United States	65203
21	Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
22	University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
23	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
24	Norris Cotton Cancer Center	Lebanon	New Hampshire	United States	03756-0002
25	Veterans Affairs Medical Center - Buffalo	Buffalo	New York	United States	14215
26	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
27	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
28	North Shore University Hospital	Manhasset	New York	United States	11030
29	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
30	New York Presbyterian Hospital - Cornell Campus	New York	New York	United States	10021
31	Mount Sinai Medical Center, NY	New York	New York	United States	10029
32	State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
33	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
34	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	Syracuse	New York	United States	13217
35	Lineberger Comprehensive Cancer Center, UNC	Chapel Hill	North Carolina	United States	27599-7295
36	Veterans Affairs Medical Center - Durham	Durham	North Carolina	United States	27705
37	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
38	CCOP - Southeast Cancer Control Consortium	Winston-Salem	North Carolina	United States	27104-4241
39	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
40	Arthur G. James Cancer Hospital - Ohio State University	Columbus	Ohio	United States	43210-1240
41	Rhode Island Hospital	Providence	Rhode Island	United States	02903
42	University of Tennessee Cancer Institute	Memphis	Tennessee	United States	38103
43	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee	United States	38104
44	Green Mountain Oncology Group	Bennington	Vermont	United States	05201
45	Vermont Cancer Center	Burlington	Vermont	United States	05401-3498
46	Veterans Affairs Medical Center - White River Junction	White River Junction	Vermont	United States	05009
47	Veterans Affairs Medical Center - Richmond	Richmond	Virginia	United States	23249
48	MBCCOP - Massey Cancer Center	Richmond	Virginia	United States	23298-0037