Chemotherapy and Rituximab With Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00020943
First received: July 11, 2001
Last updated: September 25, 2013
Last verified: September 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    Disease free and overall survival


Enrollment: 79
Study Start Date: June 2001
Study Completion Date: September 2009
Primary Completion Date: December 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 69 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00020943

  Hide Study Locations
Locations
United States, Alabama
Northeast Alabama Regional Medical Center
Anniston, Alabama, United States, 36207
Veterans Affairs Medical Center - Birmingham
Birmingham, Alabama, United States, 35233-1996
United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
Veterans Affairs Medical Center - San Diego
San Diego, California, United States, 92161
Naval Medical Center - San Diego
San Diego, California, United States, 92134-3202
UCSF Comprehensive Cancer Center
San Francisco, California, United States, 94115
Hematology/Oncology Faculty Practice
San Francisco, California, United States, 94143-0324
Veterans Affairs Medical Center - San Francisco
San Francisco, California, United States, 94121
United States, Delaware
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, District of Columbia
Lombardi Cancer Center at Georgetown University Medical Center
Washington, District of Columbia, United States, 20007
Veterans Affairs Medical Center - Washington, DC
Washington, District of Columbia, United States, 20422
Walter Reed Army Medical Center
Washington, District of Columbia, United States, 20307-5001
United States, Florida
Broward General Medical Center
Fort Lauderdale, Florida, United States, 33316
Memorial Regional Cancer Center at Memorial Regional Hospital
Hollywood, Florida, United States, 33021
CCOP - Mount Sinai Medical Center
Miami Beach, Florida, United States, 33140
Palm Beach Cancer Institute
West Palm Beach, Florida, United States, 33401
United States, Illinois
Veterans Affairs Medical Center - Chicago (Westside Hospital)
Chicago, Illinois, United States, 60612
Louis A. Weiss Memorial Hospital
Chicago, Illinois, United States, 60640
University of Chicago Cancer Research Center
Chicago, Illinois, United States, 60637-1470
CCOP - Illinois Oncology Research Association
Peoria, Illinois, United States, 61615-7828
West Suburban Center for Cancer Care
River Forest, Illinois, United States, 60305
United States, Indiana
Fort Wayne Medical Oncology and Hematology, Incorporated
Fort Wayne, Indiana, United States, 46885-5099
CCOP - Northern Indiana CR Consortium
South Bend, Indiana, United States, 46601
United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1009
United States, Kentucky
Baptist Hospital East - Louisville
Louisville, Kentucky, United States, 40207
United States, Maryland
Greenebaum Cancer Center at University of Maryland Medical Center
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
UMASS Memorial Cancer Center - University Campus
Worcester, Massachusetts, United States, 01655
United States, Michigan
Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph
Saint Joseph, Michigan, United States, 49085
United States, Minnesota
University of Minnesota Cancer Center
Minneapolis, Minnesota, United States, 55455
Veterans Affairs Medical Center - Minneapolis
Minneapolis, Minnesota, United States, 55417
United States, Missouri
Ellis Fischel Cancer Center at University of Missouri - Columbia
Columbia, Missouri, United States, 65203
Veterans Affairs Medical Center - Columbia (Truman Memorial)
Columbia, Missouri, United States, 65201
CCOP - Kansas City
Kansas City, Missouri, United States, 64131
Missouri Baptist Cancer Center
Saint Louis, Missouri, United States, 63131
Siteman Cancer Center at Barnes-Jewish Hospital
Saint Louis, Missouri, United States, 63110
United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7680
United States, Nevada
CCOP - Southern Nevada Cancer Research Foundation
Las Vegas, Nevada, United States, 89106
Veterans Affairs Medical Center - Las Vegas
Las Vegas, Nevada, United States, 89106
United States, New Hampshire
New Hampshire Oncology-Hematology, PA - Hooksett
Hooksett, New Hampshire, United States, 03106
Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756-0002
United States, New Jersey
Cooper University Hospital
Camden, New Jersey, United States, 08103
United States, New York
Veterans Affairs Medical Center - Buffalo
Buffalo, New York, United States, 14215
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263-0001
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C.
East Syracuse, New York, United States, 13057
Elmhurst Hospital Center
Elmhurst, New York, United States, 11373
Queens Cancer Center of Queens Hospital
Jamaica, New York, United States, 11432
CCOP - North Shore University Hospital
Manhasset, New York, United States, 11030
North Shore University Hospital
Manhasset, New York, United States, 11030
Mount Sinai Medical Center
New York, New York, United States, 10029
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
Veterans Affairs Medical Center - Syracuse
Syracuse, New York, United States, 13210
University Hospital at State University of New York - Upstate Medical University
Syracuse, New York, United States, 13210
United States, North Carolina
Veterans Affairs Medical Center - Asheville
Asheville, North Carolina, United States, 28805
Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27599-7295
NorthEast Oncology Associates - Concord
Concord, North Carolina, United States, 28025
Veterans Affairs Medical Center - Durham
Durham, North Carolina, United States, 27705
Duke Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
Cape Fear Valley Health System
Fayetteville, North Carolina, United States, 28302-2000
CCOP - Southeast Cancer Control Consortium
Goldsboro, North Carolina, United States, 27534-9479
Lenoir Memorial Hospital Cancer Center
Kinston, North Carolina, United States, 28503-1678
FirstHealth Moore Regional Hospital
Pinehurst, North Carolina, United States, 28374
Zimmer Cancer Center at New Hanover Regional Medical Center
Wilmington, North Carolina, United States, 28402-9025
Comprehensive Cancer Center at Wake Forest University
Winston-Salem, North Carolina, United States, 27157-1082
United States, Ohio
Arthur G. James Cancer Hospital at Ohio State University
Columbus, Ohio, United States, 43210-1240
United States, Oklahoma
Oklahoma University Medical Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224
United States, Rhode Island
Lifespan: The Miriam Hospital
Providence, Rhode Island, United States, 02906
United States, Tennessee
University of Tennessee Cancer Institute
Memphis, Tennessee, United States, 38104
Veterans Affairs Medical Center - Memphis
Memphis, Tennessee, United States, 38104
United States, Texas
Veterans Affairs Medical Center - Dallas
Dallas, Texas, United States, 75219
United States, Vermont
Green Mountain Oncology Group
Bennington, Vermont, United States, 05201
Vermont Cancer Center at University of Vermont
Burlington, Vermont, United States, 05401-3498
United States, Virginia
Martha Jefferson Hospital
Charlottesville, Virginia, United States, 22902
Virginia Oncology Associates - Norfolk
Norfolk, Virginia, United States, 23502
MBCCOP - Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke
Roanoke, Virginia, United States, 24014
United States, West Virginia
St. Mary's Medical Center
Huntington, West Virginia, United States, 25701
Puerto Rico
Puerto Rico Cancer Center at University of Puerto Rico - Medical Sciences Campus
San Juan, Puerto Rico, 00936-5067
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Lloyd Damon, MD University of California, San Francisco
  More Information

Additional Information:
Publications:
Hsi E, Jung S, Lai R, et al.: Ki67 and PIM1 expression in aggressively treated mantle cell lymphoma (MCL): A Cancer and Leukemia Group B (CALGB) 59909 correlative science study. [Abstract] J Clin Oncol 26 (Suppl 15): A-8560, 2008.
Damon LE, Johnson J, Niedzwiecki D, et al.: Immuno-chemotherapy (IC) and autologous stem cell transplant (ASCT) for untreated patients (pts) with mantle cell lymphoma (MCL): CALGB 59909. [Abstract] Blood 108 (11): A-2737, 2006.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00020943     History of Changes
Other Study ID Numbers: CDR0000068732, U10CA031946, CALGB-59909
Study First Received: July 11, 2001
Last Updated: September 25, 2013
Health Authority: United States: Federal Government

Keywords provided by Alliance for Clinical Trials in Oncology:
stage I mantle cell lymphoma
contiguous stage II mantle cell lymphoma
noncontiguous stage II mantle cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Mantle-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Carmustine
Cyclophosphamide
Liposomal doxorubicin
Rituximab
Cytarabine
Doxorubicin
Etoposide
Methotrexate
Prednisone
Vincristine
Lenograstim
Leucovorin
Levoleucovorin
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors

ClinicalTrials.gov processed this record on August 21, 2014