Donor Stem Cell Transplant After Busulfan, Fludarabine, and Antithymocyte Globulin in Treating Patients With Hematological Cancer

Study Overview
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Brief Summary
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RATIONALE: Giving chemotherapy before a donor bone marrow stem cell transplant helps stop the growth of cancer cells. Chemotherapy and antithymocyte globulin stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells 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 cyclosporine and methotrexate after transplant may stop this from happening. PURPOSE: This phase II trial is studying how well giving donor stem cell transplant together with busulfan, fludarabine, and antithymocyte globulin works in treating patients with hematological cancer.

Detailed Description
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OBJECTIVES: To investigate whether unrelated donor hematopoietic stem cell transplantation using a nonmyeloablative conditioning regimen comprising busulfan, fludarabine phosphate, and anti-thymocyte globulin can reduce treatment-related mortality in patients with hematologic malignancies. To investigate whether this regimen can be sufficiently immunosuppressive to enable engraftment of HLA-matched unrelated hematopoietic stem cells. OUTLINE: This is a multicenter study. Prior to receiving the conditioning chemotherapy regimen, all patients with acute leukemia, chronic myelogenous leukemia (CML), and high-risk myelodysplastic syndromes (chronic myelomonocytic leukemia, atypical CML, and refractory anemia with excess blasts) receive one dose of intrathecal (IT) methotrexate. These patients also receive leucovorin calcium IV or orally 4 hours after IT methotrexate and every 6 hours for a total of 8 doses. Nonmyeloablative conditioning regimen: Patients receive fludarabine phosphate IV over 30 minutes on days -7 to -2, busulfan IV over 3 hours on days -7 to -6, anti-thymocyte globulin IV over 4 hours on days -4 to -2. Allogeneic bone marrow stem cell transplantation (SCT): Patients undergo allogeneic bone marrow SCT on day 0. Graft-versus-host-disease (GVHD) prophylaxis: Patients receive cyclosporine (CSA) IV over 2-4 hours every 12 hours starting on day -1 and continuing until day 180 (CSA can be given orally every 12 hours once oral medication can be tolerated) and methotrexate IV on days 1, 3 , 6 , and 11. Once blood counts recover, patients with acute leukemia or CML in blast crisis resume IT methotrexate once every 2 weeks for a total of 3 doses. Patients also receive leucovorin calcium IV or orally 4 hours after IT methotrexate and then every 6 hours for a total of 8 doses. Patients are followed for at least 10 years after SCT.

Official Title
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Unrelated Donor Hematopoietic Stem Cell Transplantation After Nonmyeloablative Conditioning For Patients With Hematological Malignancies

Conditions
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Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Intervention / Treatment
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* Biological: anti-thymocyte globulin
* Drug: busulfan
* Drug: fludarabine phosphate
* Drug: leucovorin calcium
* Drug: methotrexate
* Procedure: allogeneic bone marrow transplantation
* Procedure: allogeneic hematopoietic stem cell transplantation
* Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of any 1 of the following: Acute leukemia Chronic myelogenous leukemia Myelodysplastic syndromes Must have an unrelated donor available who is matched for HLA-A and -B by serology and for DRB1 by molecular typing PATIENT CHARACTERISTICS: Karnofsky performance status 70-100% Bilirubin < 3.0 mg/dL Creatinine < 2.0 mg/dL AST and ALT < 3 times the upper limit of normal Not pregnant or nursing Ejection fraction ≥ 45% by MUGA scan or ECHO No major illness or organ failure No severe psychiatric disorder or mental deficiency that makes compliance with the treatment unlikely and informed consent impossible PRIOR CONCURRENT THERAPY: Not specified

Ages Eligible for Study
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Minimum Age: 15 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: anti-thymocyte globulin|nan|
|Drug: busulfan|nan|
|Drug: fludarabine phosphate|nan|
|Drug: leucovorin calcium|nan|
|Drug: methotrexate|nan|
|Procedure: allogeneic bone marrow transplantation|nan|
|Procedure: allogeneic hematopoietic stem cell transplantation|nan|
|Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-related mortality |  |  | 
| Engraftment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Regimen-related toxicities |  |  | 
| Graft-versus-host-disease |  |  | 
| Relapse |  |  | 
| Overall survival |  |  | 
| Failure-free survival |  |  | 
| 100-day transplant-related mortality |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult acute lymphoblastic leukemia in remission, recurrent adult acute lymphoblastic leukemia, untreated adult acute lymphoblastic leukemia, adult acute myeloid leukemia in remission, recurrent adult acute myeloid leukemia, untreated adult acute myeloid leukemia, acute lymphocytic leukemia, secondary acute myeloid leukemia, acute undifferentiated leukemia, mast cell leukemia, accelerated phase chronic myelogenous leukemia, blastic phase chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, meningeal chronic myelogenous leukemia, relapsing chronic myelogenous leukemia, chronic myelomonocytic leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(15;17)(q22;q12), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), de novo myelodysplastic syndromes, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, atypical chronic myeloid leukemia, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, refractory anemia with excess blasts in transformation, refractory anemia with excess blasts