A Phase II Study Of Intensive Induction Chemotherapy Followed By Autologous Stem Cell Transplantation Plus Immunotherapy For Mantle Cell Lymphoma
18 Years
69 Years
Both
Lymphoma
Trial Information
A Phase II Study Of Intensive Induction Chemotherapy Followed By Autologous Stem Cell Transplantation Plus Immunotherapy For Mantle Cell Lymphoma
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Progression Free Survival
Outcome Time Frame:
2 years
Safety Issue:
No
Principal Investigator
Lloyd Damon, MD
Investigator Role:
Study Chair
Investigator Affiliation:
University of California, San Francisco
Authority:
United States: Federal Government
Study ID:
CDR0000068732
NCT ID:
NCT00020943
Start Date:
June 2001
Completion Date:
September 2009
Related Keywords:
- Lymphoma
- 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
- Lymphoma
- Lymphoma, Mantle-Cell
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| Memorial Sloan-Kettering Cancer Center | New York, New York 10021 |
| Walter Reed Army Medical Center | Washington, District of Columbia 20307-5000 |
| University of Chicago Cancer Research Center | Chicago, Illinois 60637 |
| University of Minnesota Cancer Center | Minneapolis, Minnesota 55455 |
| Duke Comprehensive Cancer Center | Durham, North Carolina 27710 |
| CCOP - Kansas City | Kansas City, Missouri 64131 |
| CCOP - Southern Nevada Cancer Research Foundation | Las Vegas, Nevada 89106 |
| CCOP - Christiana Care Health Services | Wilmington, Delaware 19899 |
| CCOP - Mount Sinai Medical Center | Miami Beach, Florida 33140 |
| CCOP - North Shore University Hospital | Manhasset, New York 11030 |
| CCOP - Southeast Cancer Control Consortium | Winston-Salem, North Carolina 27104-4241 |
| MBCCOP - Massey Cancer Center | Richmond, Virginia 23298-0037 |
| CCOP - Illinois Oncology Research Association | Peoria, Illinois 61602 |
| Comprehensive Cancer Center at Wake Forest University | Winston-Salem, North Carolina 27157-1082 |
| Veterans Affairs Medical Center - Birmingham | Birmingham, Alabama 35233 |
| Western Pennsylvania Hospital | Pittsburgh, Pennsylvania 15224 |
| Green Mountain Oncology Group | Rutland, Vermont 05701 |
| Martha Jefferson Hospital | Charlottesville, Virginia 22901 |
| CCOP - Northern Indiana CR Consortium | South Bend, Indiana 46601 |
| Holden Comprehensive Cancer Center at University of Iowa | Iowa City, Iowa 52242-1002 |
| UMASS Memorial Cancer Center - University Campus | Worcester, Massachusetts 01605-2982 |
| Ellis Fischel Cancer Center at University of Missouri - Columbia | Columbia, Missouri 65203 |
| Siteman Cancer Center at Barnes-Jewish Hospital | Saint Louis, Missouri 63110 |
| Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center | Lebanon, New Hampshire 03756-0002 |
| Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill | Chapel Hill, North Carolina 27599-7570 |
| North Shore University Hospital | Manhasset, New York 11030 |
| Veterans Affairs Medical Center - Chicago (Westside Hospital) | Chicago, Illinois 60612 |
| Naval Medical Center - San Diego | San Diego, California 92134-3202 |
| Veterans Affairs Medical Center - San Francisco | San Francisco, California 94121 |
| Baptist Hospital East - Louisville | Louisville, Kentucky 40207 |
| CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C. | Syracuse, New York 13217 |
| Veterans Affairs Medical Center - Memphis | Memphis, Tennessee 38104 |
| Veterans Affairs Medical Center - Minneapolis | Minneapolis, Minnesota 55417 |
| Veterans Affairs Medical Center - Columbia (Truman Memorial) | Columbia, Missouri 65201 |
| Veterans Affairs Medical Center - Buffalo | Buffalo, New York 14215 |
| Veterans Affairs Medical Center - Syracuse | Syracuse, New York 13210 |
| Veterans Affairs Medical Center - Durham | Durham, North Carolina 27705 |
| Rebecca and John Moores UCSD Cancer Center | La Jolla, California 92093-0658 |
| Broward General Medical Center | Fort Lauderdale, Florida 33316 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
| Northeast Alabama Regional Medical Center | Anniston, Alabama 36207 |
| Veterans Affairs Medical Center - San Diego | San Diego, California 92161 |
| UCSF Comprehensive Cancer Center | San Francisco, California 94115 |
| Veterans Affairs Medical Center - Washington, DC | Washington, District of Columbia 20422 |
| Louis A. Weiss Memorial Hospital | Chicago, Illinois 60640 |
| West Suburban Center for Cancer Care | River Forest, Illinois 60305 |
| Fort Wayne Medical Oncology and Hematology, Incorporated | Fort Wayne, Indiana 46885-5099 |
| Veterans Affairs Medical Center - Las Vegas | Las Vegas, Nevada 89106 |
| Cooper University Hospital | Camden, New Jersey 08103 |
| Elmhurst Hospital Center | Elmhurst, New York 11373 |
| Queens Cancer Center of Queens Hospital | Jamaica, New York 11432 |
| Veterans Affairs Medical Center - Asheville | Asheville, North Carolina 28805 |
| Cape Fear Valley Health System | Fayetteville, North Carolina 28302-2000 |
| Lenoir Memorial Hospital Cancer Center | Kinston, North Carolina 28503-1678 |
| FirstHealth Moore Regional Hospital | Pinehurst, North Carolina 28374 |
| Lifespan: The Miriam Hospital | Providence, Rhode Island 02906 |
| University of Tennessee Cancer Institute | Memphis, Tennessee 38103 |
| Veterans Affairs Medical Center - Dallas | Dallas, Texas 75216 |
| Virginia Oncology Associates - Norfolk | Norfolk, Virginia 23502 |
| St. Mary's Medical Center | Huntington, West Virginia 25701 |
| Oklahoma University Medical Center | Oklahoma City, Oklahoma 73104 |
| Mount Sinai Medical Center | New York, New York 10029 |
| Vermont Cancer Center at University of Vermont | Burlington, Vermont 05405-0075 |
| Lombardi Cancer Center at Georgetown University Medical Center | Washington, District of Columbia 20007 |
| Greenebaum Cancer Center at University of Maryland Medical Center | Baltimore, Maryland 21201 |
| UNMC Eppley Cancer Center at the University of Nebraska Medical Center | Omaha, Nebraska 68198-7680 |
| New Hampshire Oncology-Hematology, PA - Hooksett | Hooksett, New Hampshire 03106 |
| NorthEast Oncology Associates - Concord | Concord, North Carolina 28025 |
| Arthur G. James Cancer Hospital at Ohio State University | Columbus, Ohio 43210-1240 |
| Oncology and Hematology Associates of Southwest Virginia, Incorporated - Roanoke | Roanoke, Virginia 24014 |
| Lakeland Cancer Care Center at Lakeland Hospital - St. Joseph | Saint Joseph, Michigan 49085 |
| New York Weill Cornell Cancer Center at Cornell University | New York, New York 10021 |
| Zimmer Cancer Center at New Hanover Regional Medical Center | Wilmington, North Carolina 28402-9025 |
| Cedars-Sinai Comprehensive Cancer Center at Cedars-Sinai Medical Center | Los Angeles, California 90048 |
| University Hospital at State University of New York - Upstate Medical University | Syracuse, New York 13210 |
| Memorial Regional Cancer Center at Memorial Regional Hospital | Hollywood, Florida 33021 |
| Missouri Baptist Cancer Center | St. Louis, Missouri 63131 |
| Palm Beach Cancer Institute | West Palm Beach, Florida 33401 |
| Hematology/Oncology Faculty Practice | San Francisco, California 94143-0324 |
