Vanderbilt-Ingram Cancer Center

The goal of this research is to study a new method of full intensity, pre-treatment (or conditioning) called CloBu4, using the drugs Clofarabine and Busulfan. These two FDA approved drugs will be used together in this new way (that is, the combination is not FDA approved). Prior to receiving a stem cell transplant, patients will get CloBu4 chemotherapy, followed by an infusion of blood stem cells collected from a donor who is a suitable match. Many transplant centers are now using a full intensity conditioning treatment called Flu/Bu4 (Fludarabine and Busulfan) as a standard pre-treatment for transplantation, but disease relapse is still a major cause of death. Clofarabine and Fludarabine are similar chemicals, but Clofarabine has a greater anti-leukemia effect (compared to Fludarabine), and may cause fewer bad side effects. CloBu4 may result in a transplant conditioning regimen with more effective leukemia control and without increased side effects (compared to FluBu4). This study will test this new conditioning treatment to learn if CloBu4 can lead to a safer and more effective stem cell transplant treatment approach for patients with non-remission AML.

Criteria
 Inclusion Criteria:

 Disease Criteria

 • AML not in remission at the time of transplant

 • "Not in remission" is defined as "greater than 5.0% bone marrow blasts by aspirate morphology," as determined by a bone marrow aspirate obtained within 2 weeks of study registration.

 • For primary induction failure patients: Patients must have failed at least 2 induction regimens.

 • For patients with relapsed disease: Patients who relapse more than 6 months after preceding remission must fail at least one reinduction regimen to be eligible. For patients in whom the preceding remission is equal to or shorter than 6 months duration, no re-induction regimen is required to qualify for this protocol.

 • If the pre-transplant bone marrow aspirate and biopsy are hypoplastic (less than 10% cellularity), and blast percentages cannot be determined, the patient is eligible if the preceding bone marrow met the above criteria.

 • Patients with peripheral circulating blasts or patients with extramedullary leukemia are eligible if bone marrow aspirate and biopsy meets the above criteria. Age and Organ Function Criteria

 • Age: 2 to 65 years in age.

 • Cardiac: LVEF ≥ 40% by MUGA (Multi Gated Acquisition) scan or echocardiogram.

 • Pulmonary: FEV1 and FVC capacity) ≥ 40% predicted, DLCO (corrected for hemoglobin) ≥ 40% of predicted.

 • Children who are unable to cooperate for pulmonary function tests (PFTs), must have no evidence of dyspnea at rest, no exercise intolerance, and not require supplemental oxygen therapy.

 • Renal: Age equal to or older than 12: The estimated creatinine clearance (CrCl) must be equal or greater than 60 mL/min/1.73 m2 as calculated by the Cockcroft-Gault Formula. Age younger than 12: Either estimated or measured CrCl should be greater than 90 ml/min/1.73m2. For estimation, Schwartz formula will be used.

 • Hepatic: Serum bilirubin ≤ 1.5 x upper limit of normal (ULN); (AST)/ ALT ≤ 2.5 x ULN; Alkaline phosphatase ≤ 2.5 x ULN

 • Performance status: Karnofsky ≥ 70%., or Lansky≥70% Consent: All patients must sign informed consent

 Exclusion Criteria:

 • Active life-threatening cancer requiring treatment other than AML

 • Non-compliant to medications.

 • No appropriate caregivers identified.

 • HIV1 (Human Immunodeficiency Virus-1) or HIV2 positive

 • Active life-threatening cancer requiring treatment other than AML

 • Uncontrolled medical or psychiatric disorders.

 • Uncontrolled infections, defined as positive blood cultures within 72 hours of study entry, or evidence of progressive infection

 • Active central nervous system (CNS) leukemia

 • Preceding allogeneic HSCT

 • Receiving intensive chemotherapy within 21 days of registration.

 • Patients with preceding primary myelofibrosis

 • Peripheral blasts > 10,000/μL at the time of registration