Feasibility and Efficacy Study of Conditioning Regimen for Allogeneic Hematopoietic Cell Transplantation (HCT) With Fludarabine, Busulfan, and Total Body Irradiation (TBI)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the OS, RFS, and TRM after HCT with low-dose total body irradiation, fludarabine, and busulfan conditioning.

Detailed Description
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Conventional allogeneic hematopoietic cell transplantation (HCT) for patients with hematological malignancies involves conditioning with high doses of systemic chemo/radiation therapy such as cyclophosphamide (CY) plus 1200 or 1000 cGy total body irradiation (TBI; CY/TBI) or busulfan (Bu) / CY (BuCy). Unfortunately, such regimens have been associated with significant toxicities, limiting their use to otherwise healthy, relatively young patients. Recently, Fludarabine plus 4 day dose of busulfan (FluBu4) containing myeloablative regimen has been introduced successfully without increasing transplant-related mortality (TRM). To improve transplant outcomes without increasing the risk of recurrence, Russell et al introduced 400cGy of TBI with antithymocyte (ATG, 4.5mg/Kg) into FluBu4 regimen with successful outcomes.

Official Title
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Prospective Phase II Clinical Trial of Myeloablative Conditioning Regimen With Fludarabine and Busulfan Plus 400 cGy Total Body Irradiation for Hematologic Malignancies

Conditions
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AML, MDS, ALL, CML, Lymphoma

Intervention / Treatment
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* Drug: fludarabine phosphate, busulfan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At least 15 years old and not more than 65 years old. ECOG performance status 0-2. Patients with AML or MDS with intermediate/unfavorable cytogenetics. Patients with ALL and CML ineligible for Cy/TBI conditioning. Patients with NHL or HD eligible to myeloablative HCT. Patients receiving unrelated BMT for AML, MDS, ALL, CML, NHL or HD. Consent form signed and dated prior to study specific procedures. Subject able to comply with the scheduled follow-up and with the management of toxicities. Exclusion Criteria: -

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Regimen<br>Conditioning regimen for AML with FLT3 mutation, AML/MDS unfavorable cytogenetic risk group, chemorefractory NHL or HD, or ALL/CML | Drug: fludarabine phosphate, busulfan<br>* Fludarabine ( 30mg/m2, iv, D-7 D-2) Busulfan (3.2mg/kg, iv, D-6 D-3) Total body irradiation (200cGy/day, D-2,-1)<br>* Other names: Fludarabine (Fludara®, Berlex Laboratories, Richmond, CA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| progression free survival |  | one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| relapse of primary disease, overall survival, and occurrence of acute/chronic GVHD |  | one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fludarabine, busulfan, total body irradiation, conditioning regimen