Chemotherapy and Rituximab With 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

NCT00020943

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Monoclonal antibodies such as rituximab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: Phase II trial to study the effectiveness of combining chemotherapy and rituximab with peripheral stem cell transplantation in treating patients who have mantle cell lymphoma.

Condition or Disease	Intervention/Treatment	Phase
Lymphoma	Biological: filgrastim Biological: rituximab Drug: carmustine Drug: cyclophosphamide Drug: cytarabine Drug: doxorubicin hydrochloride Drug: etoposide Drug: leucovorin calcium Drug: methotrexate Drug: prednisone Drug: vincristine sulfate Procedure: peripheral blood stem cell transplantation	Phase 2

Detailed Description

OBJECTIVES:

Determine the two-year progression-free survival of patients with mantle cell lymphoma treated with intensive chemotherapy and rituximab with autologous peripheral blood stem cell (PBSC) transplantation.
Determine the complete and partial response rates of patients treated with this regimen.
Determine the disease-free and overall survival of patients treated with this regimen.
Determine the autologous immune reconstitution in patients treated with this regimen.
Determine the feasibility of this regimen in this patient population.
Determine whether treatment with rituximab during autologous PBSC transplantation reduces the amount of contaminating lymphoma in the autologous PBSC product.

OUTLINE: This is a multicenter study.

Patients receive induction therapy comprising rituximab IV over 4-6 hours on day 1; methotrexate IV over 4 hours on day 2; cyclophosphamide IV over 2 hours, doxorubicin IV, and vincristine IV on day 3; and oral prednisone on days 3-7. Patients also receive leucovorin calcium IV every 6 hours beginning on day 3 and continuing until blood levels of methotrexate are safe. Filgrastim (G-CSF) is administered subcutaneously (SC) beginning on day 4 and continuing until blood counts recover.

Induction therapy repeats every 21-28 days for 2 courses in the absence of disease progression or unacceptable toxicity. Rituximab may be omitted during course 1 if circulating mantle cells are excessive. Patients may receive a third course if more than 15% persistent bone marrow involvement is documented.

Patients with stable or responding disease begin consolidation therapy 29 days after the start of the final course of induction therapy. Patients receive cytarabine IV over 2 hours twice daily and etoposide IV over 96 hours on days 1-4. Patients also receive rituximab IV over 4-6 hours on days 5 or 6 and 12 or 13 and G-CSF SC beginning on day 14 and continuing until leukapheresis is complete. Patients undergo leukapheresis beginning between days 22-25 and continuing until adequate CD34 cells are collected.

Beginning 4 weeks after recovery from consolidation therapy, patients receive high-dose therapy comprising carmustine IV over 2 hours on day -6, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 2 hours on day -2. Patients undergo autologous peripheral blood stem cell (PBSC) transplantation on day 0. Patients receive G-CSF SC beginning on day 6 and continuing until blood counts recover.

After blood counts recover and more than 35 days after autologous PBSC transplantation, patients receive rituximab IV over 4-6 hours weekly for 2 weeks.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for up to 10 years.

PROJECTED ACCRUAL: At least 45 patients will be accrued for this study within 2 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

79 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study Of Intensive Induction Chemotherapy Followed By Autologous Stem Cell Transplantation Plus Immunotherapy For Mantle Cell Lymphoma

Study Start Date :

Jun 1, 2001

Actual Primary Completion Date :

Dec 1, 2006

Actual Study Completion Date :

Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Chemo/immuno/autolog transplant Intensive chemotherapy followed by autologous stem cell transplant and immunotherapy for mantle cell lymphoma	Biological: filgrastim 5 ug/kg subQ daily day 4 until ANC >10,000 (or ANC> 5000 2X)Tx 1, 2, 4 10 ug/kg subQ daily day 14 until completion of PBSC collection Tx 3 Other Names: G-CSF Biological: rituximab 375 mg/sq m IV infusion at , or = 400 mg/hr day 1 Tx 1, 2, days 5 & 12 Tx 3, and weekly for 2 doses Tx 5 Drug: carmustine 15 mg/kg IV infusion over 2 hours Day 6, Tx 4 Drug: cyclophosphamide 2000 mg/sq m IV infusion over 2 hours Day 3, Tx 1 & 2 100 mg/kg IV infusion over 2 hours Day 2, Tx 4 Drug: cytarabine 2000 mg/sq m IV infusion BID over 2 hours x 8 doses Days 1-4, Tx 3 Other Names: ara-C Drug: doxorubicin hydrochloride 50 mg/sq m IVP Day 3, Tx 1& 2 Drug: etoposide 40 mg/kg total dose continuous IV infusion over 96 hours Days 1-4, Tx 3 Drug: leucovorin calcium 50 mg/sq m IV infusion q 6 hours x 3 doses after MTX, then 10 mg/sq m IV/PO q 6 hrs until MTX levels <0.05 uM, Tx 1 & 2 Drug: methotrexate 300 mg/sq m IV infusion over 4 hrs Day 2 Tx 1 & 2 Drug: prednisone 100 mg/sq m PO Days 3-7, Tx 1 & 2 Drug: vincristine sulfate 1.4 mg/sq m IVP Day 3, Tx 1 & 2 Procedure: peripheral blood stem cell transplantation Stem cells collected during Tx 3 will be transfused follwing chemotx in Tx 4

Arm

Intervention/Treatment

Experimental: Chemo/immuno/autolog transplant

Intensive chemotherapy followed by autologous stem cell transplant and immunotherapy for mantle cell lymphoma

Biological: filgrastim

5 ug/kg subQ daily day 4 until ANC >10,000 (or ANC> 5000 2X)Tx 1, 2, 4 10 ug/kg subQ daily day 14 until completion of PBSC collection Tx 3

Other Names:

G-CSF

Biological: rituximab

375 mg/sq m IV infusion at , or = 400 mg/hr day 1 Tx 1, 2, days 5 & 12 Tx 3, and weekly for 2 doses Tx 5

Drug: carmustine

15 mg/kg IV infusion over 2 hours Day 6, Tx 4

Drug: cyclophosphamide

2000 mg/sq m IV infusion over 2 hours Day 3, Tx 1 & 2 100 mg/kg IV infusion over 2 hours Day 2, Tx 4

Drug: cytarabine

2000 mg/sq m IV infusion BID over 2 hours x 8 doses Days 1-4, Tx 3

Other Names:

ara-C

Drug: doxorubicin hydrochloride

50 mg/sq m IVP Day 3, Tx 1& 2

Drug: etoposide

40 mg/kg total dose continuous IV infusion over 96 hours Days 1-4, Tx 3

Drug: leucovorin calcium

50 mg/sq m IV infusion q 6 hours x 3 doses after MTX, then 10 mg/sq m IV/PO q 6 hrs until MTX levels <0.05 uM, Tx 1 & 2

Drug: methotrexate

300 mg/sq m IV infusion over 4 hrs Day 2 Tx 1 & 2

Drug: prednisone

100 mg/sq m PO Days 3-7, Tx 1 & 2

Drug: vincristine sulfate

1.4 mg/sq m IVP Day 3, Tx 1 & 2

Procedure: peripheral blood stem cell transplantation

Stem cells collected during Tx 3 will be transfused follwing chemotx in Tx 4

Outcome Measures

Primary Outcome Measures

Progression Free Survival [2 years]

Secondary Outcome Measures

Response [2 years]
Survival [5 years]
Disease free and overall survival

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 69 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed mantle cell lymphoma
Presenting with at least one of the following:
Coexpression of CD20 (or CD19) and CD5 and a lack of CD23 expression by immunophenotyping
Positive for cyclin D1 by immunostaining
Presence of t(11,14) by cytogenetic analysis
Molecular evidence of bcl-1/IgH rearrangement
Stage I-IV disease
Stage III or IV if nodular histology mantle cell lymphoma present
Any stage for other mantle cell histologies
No mantle zone histology
No active CNS disease
No symptomatic meningeal lymphoma
No known CNS parenchymal lymphoma
Lumbar puncture showing mantle cell lymphoma allowed
Bidimensionally measurable disease greater than 1 cm
Nonmeasurable disease includes the following:
Bone lesions
Leptomeningeal disease
Ascites
Pleural/pericardial effusion
Inflammatory breast disease
Lymphangitis cutis/pulmonis
Abdominal masses not confirmed and followed by imaging techniques
Cystic lesions
Lesions in a previously irradiated area

PATIENT CHARACTERISTICS:

Age:

18 to 69

Performance status:

Not specified

Life expectancy:

Not specified

Hematopoietic:

Not specified

Hepatic:

Hepatitis B surface antigen and hepatitis C antibody positive patients must meet all of the following criteria:
Bilirubin no greater than 2 times upper limit of normal (ULN)
AST no greater than 3 times ULN
Liver biopsy shows no greater than grade 2 fibrosis and no cirrhosis

Renal:

Creatinine no greater than 2.0 mg/dL

Cardiovascular:

LVEF at least 45% by MUGA or echocardiogram

Other:

No known hypersensitivity to murine products
HIV negative
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

No more than 1 prior dose of rituximab

Chemotherapy:

No more than 1 prior cycle of chemotherapy
At least 3 weeks since prior chemotherapy
No other concurrent chemotherapeutic agents

Endocrine therapy:

No chronic use of oral corticosteroids for ongoing medical condition
No concurrent hormonal therapy except for non-lymphoma-related conditions (e.g., insulin for diabetes)
Other concurrent corticosteroids for adrenal failure, diffuse alveolar hemorrhage, carmustine pneumonitis, or as an anti-emetic allowed

Radiotherapy:

No prior radiotherapy for mantle cell lymphoma
Concurrent palliative radiotherapy allowed
Concurrent cranial radiotherapy for asymptomatic meningeal lymphoma allowed

Surgery:

At least 2 weeks since prior major surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northeast Alabama Regional Medical Center	Anniston	Alabama	United States	36207
2	Veterans Affairs Medical Center - Birmingham	Birmingham	Alabama	United States	35233-1996
3	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
4	Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
5	Naval Medical Center - San Diego	San Diego	California	United States	92134-3202
6	Veterans Affairs Medical Center - San Diego	San Diego	California	United States	92161
7	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
8	Veterans Affairs Medical Center - San Francisco	San Francisco	California	United States	94121
9	Hematology/Oncology Faculty Practice	San Francisco	California	United States	94143-0324
10	CCOP - Christiana Care Health Services	Newark	Delaware	United States	19713
11	Lombardi Cancer Center at Georgetown University Medical Center	Washington	District of Columbia	United States	20007
12	Walter Reed Army Medical Center	Washington	District of Columbia	United States	20307-5001
13	Veterans Affairs Medical Center - Washington, DC	Washington	District of Columbia	United States	20422
14	Broward General Medical Center	Fort Lauderdale	Florida	United States	33316
15	Memorial Regional Cancer Center at Memorial Regional Hospital	Hollywood	Florida	United States	33021
16	CCOP - Mount Sinai Medical Center	Miami Beach	Florida	United States	33140
17	Palm Beach Cancer Institute	West Palm Beach	Florida	United States	33401
18	Veterans Affairs Medical Center - Chicago (Westside Hospital)	Chicago	Illinois	United States	60612
19	University of Chicago Cancer Research Center	Chicago	Illinois	United States	60637-1470
20	Louis A. Weiss Memorial Hospital	Chicago	Illinois	United States	60640
21	CCOP - Illinois Oncology Research Association	Peoria	Illinois	United States	61615-7828
22	West Suburban Center for Cancer Care	River Forest	Illinois	United States	60305
23	Fort Wayne Medical Oncology and Hematology, Incorporated	Fort Wayne	Indiana	United States	46885-5099
24	CCOP - Northern Indiana CR Consortium	South Bend	Indiana	United States	46601
25	Holden Comprehensive Cancer Center at University of Iowa	Iowa City	Iowa	United States	52242-1009
26	Baptist Hospital East - Louisville	Louisville	Kentucky	United States	40207
27	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
28	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
29	UMASS Memorial Cancer Center - University Campus	Worcester	Massachusetts	United States	01655
30	Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph	Saint Joseph	Michigan	United States	49085
31	Veterans Affairs Medical Center - Minneapolis	Minneapolis	Minnesota	United States	55417
32	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
33	Veterans Affairs Medical Center - Columbia (Truman Memorial)	Columbia	Missouri	United States	65201
34	Ellis Fischel Cancer Center at University of Missouri - Columbia	Columbia	Missouri	United States	65203
35	CCOP - Kansas City	Kansas City	Missouri	United States	64131
36	Siteman Cancer Center at Barnes-Jewish Hospital	Saint Louis	Missouri	United States	63110
37	Missouri Baptist Cancer Center	Saint Louis	Missouri	United States	63131
38	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-7680
39	CCOP - Southern Nevada Cancer Research Foundation	Las Vegas	Nevada	United States	89106
40	Veterans Affairs Medical Center - Las Vegas	Las Vegas	Nevada	United States	89106
41	New Hampshire Oncology-Hematology, PA - Hooksett	Hooksett	New Hampshire	United States	03106
42	Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756-0002
43	Cooper University Hospital	Camden	New Jersey	United States	08103
44	Veterans Affairs Medical Center - Buffalo	Buffalo	New York	United States	14215
45	Roswell Park Cancer Institute	Buffalo	New York	United States	14263-0001
46	CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.	East Syracuse	New York	United States	13057
47	Elmhurst Hospital Center	Elmhurst	New York	United States	11373
48	Queens Cancer Center of Queens Hospital	Jamaica	New York	United States	11432
49	CCOP - North Shore University Hospital	Manhasset	New York	United States	11030
50	North Shore University Hospital	Manhasset	New York	United States	11030
51	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
52	New York Weill Cornell Cancer Center at Cornell University	New York	New York	United States	10021
53	Mount Sinai Medical Center	New York	New York	United States	10029
54	University Hospital at State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
55	Veterans Affairs Medical Center - Syracuse	Syracuse	New York	United States	13210
56	Veterans Affairs Medical Center - Asheville	Asheville	North Carolina	United States	28805
57	Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill	Chapel Hill	North Carolina	United States	27599-7295
58	NorthEast Oncology Associates - Concord	Concord	North Carolina	United States	28025
59	Veterans Affairs Medical Center - Durham	Durham	North Carolina	United States	27705
60	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
61	Cape Fear Valley Health System	Fayetteville	North Carolina	United States	28302-2000
62	CCOP - Southeast Cancer Control Consortium	Goldsboro	North Carolina	United States	27534-9479
63	Lenoir Memorial Hospital Cancer Center	Kinston	North Carolina	United States	28503-1678
64	FirstHealth Moore Regional Hospital	Pinehurst	North Carolina	United States	28374
65	Zimmer Cancer Center at New Hanover Regional Medical Center	Wilmington	North Carolina	United States	28402-9025
66	Comprehensive Cancer Center at Wake Forest University	Winston-Salem	North Carolina	United States	27157-1082
67	Arthur G. James Cancer Hospital at Ohio State University	Columbus	Ohio	United States	43210-1240
68	Oklahoma University Medical Center	Oklahoma City	Oklahoma	United States	73104
69	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224
70	Lifespan: The Miriam Hospital	Providence	Rhode Island	United States	02906
71	University of Tennessee Cancer Institute	Memphis	Tennessee	United States	38104
72	Veterans Affairs Medical Center - Memphis	Memphis	Tennessee	United States	38104
73	Veterans Affairs Medical Center - Dallas	Dallas	Texas	United States	75219
74	Green Mountain Oncology Group	Bennington	Vermont	United States	05201
75	Vermont Cancer Center at University of Vermont	Burlington	Vermont	United States	05401-3498
76	Martha Jefferson Hospital	Charlottesville	Virginia	United States	22902
77	Virginia Oncology Associates - Norfolk	Norfolk	Virginia	United States	23502
78	MBCCOP - Massey Cancer Center	Richmond	Virginia	United States	23298-0037
79	Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke	Roanoke	Virginia	United States	24014
80	St. Mary's Medical Center	Huntington	West Virginia	United States	25701
81	Puerto Rico Cancer Center at University of Puerto Rico - Medical Sciences Campus	San Juan		Puerto Rico	00936-5067