Chemotherapy and Rituximab With Peripheral Stem Cell Transplantation in Treating Patients With Mantle Cell Lymphoma
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
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 |
- Progression Free Survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- 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 |
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
Show 81 Study Locations| Study Chair: | Lloyd Damon, MD | University of California, San Francisco |
More Information
Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Monica M Bertagnolli, Cancer and Leukemia Group B |
| ClinicalTrials.gov Identifier: | NCT00020943 History of Changes |
| Other Study ID Numbers: | CDR0000068732, U10CA031946, CALGB-59909 |
| Study First Received: | July 11, 2001 |
| Last Updated: | March 31, 2011 |
| Health Authority: | United States: Federal Government |
Keywords provided by Cancer and Leukemia Group B:
|
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 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 Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on June 17, 2013