Busulfan-fludarabine Conditioning and T-cell Depleted Allogeneic Stem Cell Transplantation for Patients With Advanced Hematologic Malignancies

Study Overview
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Brief Summary
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The purpose of this study is: To establish the maximally tolerated dose (MTD) of intravenous busulfan (Busulfan®) in combination with fludarabine as conditioning regimen for transplantation with in-vivo T-cell depletion. To evaluate disease free and overall survival after this conditioning regimen in patients with advanced acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). To evaluate potential pharmacogenomic determinants of toxicity of this regimen. To evaluate potential pharmacogenomic determinants of efficacy of this regimen.

Official Title
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A Phase I-II Study of Busulfan-fludarabine Conditioning and T-cell Depleted Allogeneic Stem Cell Transplantation for Patients With Advanced Hematologic Malignancies

Conditions
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Leukemia, Lymphoma, Myeloma

Intervention / Treatment
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* Drug: Busulfan
* Drug: Fludarabine
* Drug: Campath
* Procedure: Stem Cell Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Phase I portion: Relapsed or refractory acute myelogenous or lymphoid leukemia. Chronic myelogenous leukemia in accelerated phase or blast-crisis. Recurrent or refractory malignant lymphoma or Hodgkin's disease Recurrent or refractory multiple myeloma. Chronic lymphocytic leukemia, relapsed or with poor prognostic features. Myeloproliferative disorder (polycythemia vera, myelofibrosis) with transformation Myelodysplastic syndromes with more than 5% blasts. Phase II portion: AML with active disease or beyond CR2. MDS with more than 5% blasts. Exclusion Criteria: Clinical progression. Such patients may be treated on other treatment protocols or at the investigator's discretion. Such patients will continue to be monitored for survival and, may be asked to continue to provide specimens for studies of minimal residual disease and immune reconstitution as other treatments are recommended.

Ages Eligible for Study
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Minimum Age: 18 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

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Busulfan and fludarabine<br>Intravenous busulfan (Busulfan®) in combination with fludarabine | Drug: Busulfan<br>* Daily intravenous dosing to target AVC<br>Drug: Fludarabine<br>* Fludarabine dosing will be based on actual body weight. Fludarabine will be infused over 30 minutes before busulfan treatment dose.<br>Drug: Campath<br>* All patients will receive premedication for Campath (daily doses of 20 mg are repeated for up to five times).<br>Procedure: Stem Cell Transplant<br>* Infusion of bone marrow and donors(related/ unrelated).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | Maximally tolerated area under the curve of intravenous busulfan (Busulfan®) in combination with fludarabine as conditioning regimen for transplantation with in-vivo T-cell depletion. The number reported will be an Area Under the Curve (AUC) measure reported in µmol-min/L. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival | Overall Survival measured as median survival in days | 5 years | 
| Disease Free Survival | Disease Free Survival measured by median survival time in days | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancers of the blood