Allo BMT Using Matched Related/Unrelated Donors With FluBu and HiCY

Study Overview
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Brief Summary
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The purpose of this research is to find the most effective and least toxic way to prevent GVHD after BMT.

Detailed Description
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A person who has cancer of the blood or lymph glands can be treated by bone marrow transplantation (BMT). BMT has developed over several decades of research on both animal and human subjects as an effective treatment of various malignant and nonmalignant hematologic diseases. Many hematologic malignancies can be successfully treated with a combination of high-dose chemotherapy or chemo-radiotherapy and transplantation of allogeneic bone marrow or peripheral blood stem cells (alloBMT) However, a possible side effect of BMT is graft versus host disease (GVHD). GVHD occurs when cells of the donor's immune system, which are present in the bone marrow, attack the BMT recipient's normal tissue. Prevention of GVHD is important for the success of the bone marrow transplant. This research is being done to find the most effective and least toxic way to prevent GVHD after BMT

Official Title
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Trial of Allogeneic BMT for Hematologic Malignancies Using HLA-matched Related or Unrelated Donors With Fludarabine and IV Busulfan as Pre-transplant Conditioning Followed by Post-transplant Immunosuppression With High-dose Cyclophosphamide

Conditions
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Lymphoma, Multiple Myeloma, Leukemia, Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Busulfan, Fludarabine, Cytoxan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ages between 0 to and 65 years of age. Patient must have a genotypically HLA-identical sibling, a phenotypically matched first-degree relative or an unrelated matched donor. Acute lymphocytic leukemia (ALL) in CR1 with high risk features Acute myeloid leukemia (AML) in CR1 with high risk features defined as: i. Greater than 1 cycle of induction therapy required to achieve remission, ii. Preceding myelodysplastic syndrome (MDS) other than myelofibrosis, secondary AML iii. Presence of Flt3 mutations or internal tandem duplications, iv. FAB M6 or M7 classification or adverse cytogenetics for overall survival such as those associated with MDS, M6, M7 leukemia, or v. Complex karyotype [> 3 abnormalities] Acute Leukemias in 2nd or greater remission Refractory or Relapsed AML AML transformed from MDS Myelodysplastic syndrome (MDS) beyond refractory anemia Chronic myeloid leukemia (CML) Chronic myelomonocytic leukemia Philadelphia-negative myeloproliferative disorder Relapsed chemotherapy-sensitive Hodgkin's or Non-Hodgkin's lymphoma Multiple Myeloma-Stage III Exclusion Criteria: Prior autologous or allogeneic stem cell transplant. Performance status greater than 2 Active infection. Inadequate cardiac function; arrythmias or symptomatic cardiac disease. Inadequate pulmonary function; FEV1, FVC, DLCO <50% of predicted Inadequate Serum creatinine clearance <60 InadequatebHepatic function Positive serology for HIV-1, 2 or HTLV-1, 2. Pregnancy. Female patient must have negative pregnancy test

Ages Eligible for Study
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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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Busulfan, Fludarabine, Cytoxan|Busulfan once a day for 4 days Fludarabine once a day for 4 days Bone marrow transplant Cytoxan two doses|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To Determine the Optimal Regimen of Post-graft Immunosuppression With High-dose Cy Following Fludarabine, Busulfan, and Transplantation of Fully HLA-matched Bone Marrow That Leads to an Acceptable Incidence of Grades III/IV Acute GVHD | Percentage of participants with grade III-IV acute graft versus host disease (GVHD). GVHD is graded on a combination of skin symptoms (rash), gut symptoms (diarrhea), and liver symptoms (using a lab test called bilirubin). Grades range from I to IV, where I is the least severe and IV is the most severe. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Busulfan, Acute lymphocytic leukemia (ALL), Acute myeloid leukemia (AML), Acute Leukemia, Refractory or Relapsed AML, Myelodysplastic syndrome (MDS), Chronic myeloid leukemia (CML), Chronic myelomonocytic leukemia, Hodgkin's Lymphoma, Non-Hodgkin's lymphoma, Philadelphia-negative myeloproliferative disorder, Hematologic Malignancies, Transplantation, Fludarabine, Cytoxan, Bone Marrow, Allogeneic, Related donor, unrelated donor