Blood Stem Cell Transplantation for the Treatment of Older Patients With Acute Myelogenous Leukemia

Study Overview
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Brief Summary
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The prognosis for older individuals with acute myelogenous leukemia (AML) has been historically poor, with 2 year disease-free survival rates < 20% reported. Younger patients with AML in first complete remission are routinely treated using a full intensity (myelo-ablative) chemotherapy followed by a blood stem cell transplant. For the older patient with AML, full intensity therapy transplants have been greatly limited by increased rates of toxic effects related to this type of conditioning regimen. Reduced intensity (non-myeloablative) conditioning regimens have been used in a number of clinical settings, including AML therapy, to lessen the regimen related toxicity in the older patient. Recent data from the University of Michigan Blood and Marrow Transplant Program suggests improved survival for individuals > 55 years in age undergoing reduced intensity, transplants from unrelated donors. This study will investigate the safety and efficacy of this treatment option for older patients with AML, with the primary goal being to improve the survival and lifespan for older patients with AML.

Official Title
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Hematopoietic Stem Cell Transplantation for the Treatment of Older Patients With Acute Myelogenous Leukemia

Conditions
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Acute Myelogenous Leukemia

Intervention / Treatment
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* Drug: Fludarabine
* Drug: Busulfan
* Radiation: Total Body Irradiation
* Procedure: Stem Cell Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Study Registration: Age 55 - 70 years. Subjects diagnosed with AML (> 20% myeloblasts). For Proceeding to Transplant: Subjects must be in either complete remission (CR) or partial remission (PR) within 14 days prior to admission. Subjects must be > 21 days since completion of prior systemic chemotherapy or radiation therapy (including craniospinal XRT), prior to admission . Organ function requirements for a reduced intensity (FluBu2) regimen (must be met within 21 days of admission): Cardiac: LV Ejection Fraction > 40% on MUGA or Echocardiogram. Pulmonary: FEV1 and FVC > 40% predicted, DLCO > 40% of predicted. Renal: Serum creatinine < 2.0 mg/dl. Not on hemodialysis or continuous veno-venous filtration (CVVH). Hepatic: serum total bilirubin < 3.0 mg/dl and AST / ALT < 4x ULN Karnofsky > 60%. Organ function requirements for a full intensity (FluBu4) regimen (must be met within 21 days of admission): Cardiac: LV Ejection Fraction > 40% on MUGA or Echocardiogram. Pulmonary: FEV1 and FVC > 50% predicted, DLCO (corrected for hemoglobin) > 50% of predicted. Renal: serum creatinine < 2.0 mg/dl. Not on hemodialysis or continuous veno-venous filtration (CVVH) Hepatic: serum total bilirubin < 3.0 mg/dl and AST / ALT < 4x ULN. Karnofsky > 60%. Exclusion Criteria: For Study Registration: Subjects with M3 AML (FAB classification) For Proceeding to Transplant: Subjects who exhibit signs of progressive disease (> 20% blasts) within 14 days prior to admission for transplant Patients with an uncontrolled viral or fungal infection within the prior 28 days. Patients who are HIV1 or HIV2 positive. Uncontrollable medical or psychiatric disorder

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 70 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: Fludarabine plus Busulfan (CR)<br>Patients in CR will receive a reduced intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu2). | Drug: Fludarabine<br>* Fludarabine (40 mg/m2/day x 4 days)<br>Drug: Busulfan<br>* Busulfan (3.2 mg/m2/day x 2 days or x 4 days).<br>Radiation: Total Body Irradiation<br>* Patients who receive Busulfan 3.2 mg/m2/day x 2 days and a mismatched allograft (7/8 HLA match) will also receive 200 cGy of total body irradiation (TBI) pre-transplant.<br>Procedure: Stem Cell Transplant<br>* Allogeneic stem cell transplant from related or unrelated donor<br>|
| Experimental: Fludarabine plus Busulfan (PR)<br>Patients in PR will receive a full intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu4). | Drug: Fludarabine<br>* Fludarabine (40 mg/m2/day x 4 days)<br>Drug: Busulfan<br>* Busulfan (3.2 mg/m2/day x 2 days or x 4 days).<br>Procedure: Stem Cell Transplant<br>* Allogeneic stem cell transplant from related or unrelated donor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Relapse Free Survival at 1 Year | The primary objective was to determine the 1 year relapse free survival rate (RFS) for individuals > 55 years in age with Acute myeloid leukemia (AML) in Complete Remission (CR) or Partial Remission (PR) who undergo a 7-8/8 HLA- matched unrelated donor transplant using a reduced intensity regimen. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Alive at 1 Year | One of the secondary objectives was to determine overall survival for patients > 55 years in age with AML undergoing full or reduced transplant with the best available donor. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML