Methotrexate |
Rheumatrex; Trexall |
Clinical Trial: Fludarabine and Melphalan Followed by Tacrolimus and Methotrexate in Treating Patients Who Are Undergoing a Donor Stem Cell Transplant for Relapsed Lymphoma
This study is not yet open for patient recruitment.
Purpose
RATIONALE: A peripheral stem cell transplant or bone marrow transplant may be able to replace blood-forming cells that were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an immune response against the body''''s normal cells. Giving fludarabine together with melphalan followed by tacrolimus and methotrexate 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 | Intervention | Phase |
|---|---|---|
| adult Hodgkin''''s lymphoma adult non-Hodgkin''''s lymphoma | Drug: fludarabine Drug: melphalan Drug: methotrexate Drug: tacrolimus Procedure: allogeneic bone marrow transplantation Procedure: biological response modifier therapy Procedure: bone marrow ablation with stem cell support Procedure: bone marrow transplantation Procedure: chemotherapy Procedure: graft versus host disease prophylaxis/therapy Procedure: peripheral blood stem cell transplantation Procedure: supportive care/therapy | Phase II |
MedlinePlus related topics: Hodgkin''''s Disease; Lymphoma
Study Type: Interventional
Study Design: Treatment
Official Title: Phase II Study of 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 in Patients with Relapsed Hodgkin''''s Or Non-Hodgkin''''s Lymphoma After Prior Autologous Stem Cell Transplantation
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 5. 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.
Eligibility
DISEASE CHARACTERISTICS:
- Diagnosis of lymphoma of 1 of the following types:
- Diffuse large B-cell lymphoma
- Follicular lymphoma
- Grades 1, 2, or 3
- Primary mediastinal lymphoma
- Mantle cell lymphoma
- Small lymphocytic lymphoma
- Hodgkin''''s lymphoma
- Transformed lymphoma
- Relapsed after prior autologous bone marrow transplantation (BMT)
- More than 180 days post BMT
- Received ≥ 1 course of chemotherapy after BMT relapse
- Achieved a complete response OR a partial response to chemotherapy
- Largest residual tumor dimension ≤ 2 cm
- No clinical or laboratory evidence of CNS involvement by lymphoma
- HLA-identical donor available, meeting 1 of the following criteria:
- 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
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
- None of the following within the past 6 months:
- Myocardial infarction
- Unstable angina
- Uncontrolled atrial fibrillation
- 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
Location and Contact Information
Patrick J. Stiff, MD, Loyola University
Scott E. Smith, MD, PhD, Study Chair, Loyola University
More Information
Clinical trial summary from the National Cancer Institute''''s PDQ® database
Record last reviewed: July 2005
Last Updated: July 25, 2005
Record first received: July 20, 2005
ClinicalTrials.gov Identifier: NCT00121186
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-07-26
Resources
- Methotrexate (Drug Digest)
- Methotrexate (Cleveland Clinic)

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