S0501 Fludarabine, Melphalan, and Donor Stem Cell Transplant Followed By Tacrolimus and Methotrexate in Treating Patients for Relapsed Lymphoma
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| ClinicalTrials.gov Identifier: NCT00121186 |
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Recruitment Status :
Terminated
(poor accrual)
First Posted : July 21, 2005
Results First Posted : April 3, 2012
Last Update Posted : April 3, 2012
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RATIONALE: Giving low doses of chemotherapy, such as fludarabine and melphalan, before a donor bone marrow or peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus and methotrexate after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving fludarabine together with melphalan followed by tacrolimus and methotrexate works in treating patients who are undergoing a donor stem cell transplant for relapsed lymphoma.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Lymphoma | Drug: fludarabine phosphate Drug: melphalan Drug: methotrexate Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Procedure: peripheral blood stem cell transplantation | Phase 2 |
OBJECTIVES:
- Determine the 1-year progression-free and overall survival rate in patients with relapsed Hodgkin's or non-Hodgkin's lymphoma after prior autologous stem cell transplantation treated with a nonmyeloablative conditioning regimen comprising fludarabine and melphalan followed by allogeneic bone marrow or peripheral blood stem cell transplantation and immunosuppression comprising tacrolimus and methotrexate.
- Determine treatment-related mortality in patients treated with this regimen.
- Determine the toxic effects of this regimen in these patients.
- Determine engraftment of donor hematopoietic stem cells, as measured by hematopoietic recovery and donor-derived hematopoiesis (determined by T cell and neutrophil specific chimerism) at 2, 3, 6, and 12 months, in patients treated with this regimen.
- Determine the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen.
OUTLINE: This is a multicenter study. Patients are stratified according to diagnosis (Hodgkin's lymphoma vs non-Hodgkin's lymphoma).
Patients receive fludarabine IV over 1 hour on days -6 to -2 and melphalan IV over 15-20 minutes on days -3 and -2. Patients undergo allogeneic peripheral blood stem cell or bone marrow transplantation on day 0. Patients receive oral tacrolimus twice daily beginning on day -3 and continuing until day 100 followed by a taper to day 180. Patients also receive methotrexate IV on days 1, 3, and 7. Treatment continues in the absence of disease progression or unacceptable toxicity.
After completion of study transplantation, patients are followed at 1 and 3 months, 1 year, and then annually for up to 4 years.
PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study within 2 years.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | Nonmyeloablative Allogeneic Stem Cell Transplantation For Relapsed Hodgkin's or Non-Hodgkin's Lymphoma After Autologous Transplantation ( A BMT Study) |
| Study Start Date : | July 2005 |
| Actual Primary Completion Date : | January 2008 |
| Actual Study Completion Date : | December 2011 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Nonmyeloablative allogeneic stem cell transplant
Patients are given fludarabine 30 mg/m^2 on days -6 to -2 and melphalan 70 mg/m^2 on days -3 and -2, then transplanted with donor peripheral blood stem cells or harvested bone marrow stem cells on day 0. Patients are then given post-transplant immunosuppression consisting of tacrolimus 0.06 mg/kg/day on days -3 to 100 and methotrexate 5 mg/m^2 on days 1, 3, and 7.
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Drug: fludarabine phosphate
30 mg/m^2 on days -6 to -2 (2-6 days before transplant). Drug: melphalan 70 mg/m^2 on days -3 and -2 (2-3 days before transplant). Drug: methotrexate 5 mg/m^2 on days 1, 3, and 7 post-transplant. Drug: tacrolimus 0.03 mg/kg bid on days -3 to 100 post-transplant. Procedure: allogeneic bone marrow transplantation if donor bone marrow stem cells are harvested Procedure: peripheral blood stem cell transplantation if donor peripheral blood stem cells are harvested |
- Progression-free Survival [ Time Frame: 1, 3, and 12 months after protocol treatment, then every 3 months for 1 year, every 6 months for year 2, then annually thereafter until 5 years after registration ]PFS rate at 1 year.
- Overall Survival [ Time Frame: 1, 3, and 12 months after protocol treatment, then every 3 months for 1 year, every 6 months for year 2, then annually thereafter until 5 years after registration ]OS rate at 1 year.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
DISEASE CHARACTERISTICS:
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Diagnosis of lymphoma of 1 of the following types:
- Diffuse large B-cell lymphoma
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Follicular lymphoma
- Grades 1, 2, or 3
- Primary mediastinal lymphoma
- Mantle cell lymphoma
- Small lymphocytic lymphoma
- Hodgkin's lymphoma
- Transformed lymphoma
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Relapsed after prior autologous bone marrow transplantation (BMT)
- More than 180 days post BMT
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Received ≥ 1 course of chemotherapy after BMT relapse
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Achieved a complete response OR a partial response to chemotherapy
- Largest residual tumor dimension ≤ 2 cm
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- No clinical or laboratory evidence of CNS involvement by lymphoma
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HLA-identical donor available, meeting 1 of the following criteria:
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Sibling donor with 5/6 or 6/6 alleles matching by genotyping
- No monozygotic identical twins
- Unrelated donor with 10/10 alleles matching by genotyping
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PATIENT CHARACTERISTICS:
Age
- 18 and over
Performance status
- Zubrod 0-2
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- Not specified
Renal
- Not specified
Cardiovascular
- LVEF ≥ 40% by MUGA or 2-D echocardiogram (2-D ECHO)
- No significant cardiac abnormalities by MUGA or 2-D ECHO
- No uncompensated coronary artery disease by ECG or physical exam
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None of the following within the past 6 months:
- Myocardial infarction
- Unstable angina
- Uncontrolled atrial fibrillation
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None of the following within the past 3 months:
- Severe peripheral vascular disease
- Venous stasis ulcers
- Deep venous or arterial thrombosis
- No uncontrolled hypertension
Pulmonary
- DLCO (corrected) and total lung capacity ≥ 40% of predicted
- No requirement for continuous supplemental oxygen
Other
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- HIV negative
- No AIDS
- No active bacterial, viral, or fungal infection
- No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
- No history of uncontrolled seizures
- No diabetic ulcers within the past 3 months
PRIOR CONCURRENT THERAPY:
Biologic therapy
- See Disease Characteristics
- No more than 1 prior bone marrow transplantation
Chemotherapy
- See Disease Characteristics
- More than 21 days since prior chemotherapy and recovered
Endocrine therapy
- Not specified
Radiotherapy
- More than 4 weeks since prior radiotherapy
Surgery
- More than 4 weeks since prior major surgery except placement of a venous access device
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00121186
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| Study Chair: | Patrick J. Stiff, MD | Loyola University | |
| Study Chair: | Scott E. Smith, MD, PhD, FACP | Loyola University |
| Responsible Party: | Southwest Oncology Group |
| ClinicalTrials.gov Identifier: | NCT00121186 |
| Other Study ID Numbers: |
CDR0000435930 S0501 ( Other Identifier: SWOG ) U10CA032102 ( U.S. NIH Grant/Contract ) |
| First Posted: | July 21, 2005 Key Record Dates |
| Results First Posted: | April 3, 2012 |
| Last Update Posted: | April 3, 2012 |
| Last Verified: | March 2012 |
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recurrent adult Hodgkin lymphoma recurrent small lymphocytic lymphoma recurrent mantle cell lymphoma recurrent grade 1 follicular lymphoma |
recurrent grade 2 follicular lymphoma recurrent grade 3 follicular lymphoma recurrent adult diffuse large cell lymphoma |
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Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Methotrexate Fludarabine phosphate Fludarabine Melphalan Tacrolimus Abortifacient Agents, Nonsteroidal Abortifacient Agents Reproductive Control Agents |
Physiological Effects of Drugs Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Dermatologic Agents Enzyme Inhibitors Folic Acid Antagonists Immunosuppressive Agents Immunologic Factors Antirheumatic Agents Nucleic Acid Synthesis Inhibitors Calcineurin Inhibitors Antineoplastic Agents, Alkylating Alkylating Agents |