Multi-center Study of Myeloablative Allo Stem Cell Transplant for Non-remission AML Using CloBu4 Regimen
Condition: Acute Myeloblastic Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Clofarabine/Busulfan x 4; Peripheral blood stem cell transplant
Intervention description: Clofarabine IV dose level: 40 mg/m2/day x 5 days
Busulfan IV dose level: 3.2 mg/kg daily x 4 days; Peripheral blood stem cell transplant, after pre-conditioning drug treatment
Intervention MeSH terms: Busulfan; Clofarabine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 75.0
Sex: All
Minimum age: 2 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: AML

Summary:

      Although transplant results for AML in complete remission (CR) at the time of transplant have
      improved, transplant results for non-remission AML have been quite poor. Most multi-center
      studies have focused on standard risk AML patients and not many studies have been done in
      this population of patients with non-remission AML. There are a large number of older
      patients with non-remission AML because the complete remission rate with induction
      chemotherapy decreases with age. Such older patients do not tolerate conventional full
      intensity conditioning regimens. Thus, an effective and tolerable conditioning regimen for
      non-remission AML is a great unmet need for current transplant practice.

      From the investigators earlier study, it is suggested that replacing Fludarabine of standard
      FluBu4 regimen by Clofarabine (a related drug with much more potent anti-leukemia effect) in
      the transplant conditioning regimen may potentiate the anti-tumor activity of the
      conditioning regimen without adding significant toxicity, a goal of new conditioning regimen
      development.

      The investigators expect to enroll a total of 75 patients from about fifteen sites. The
      investigators main objective is to confirm both the safety and efficacy as measured by
      one-year overall survival, of the CloBu4 combination as full intensity conditioning for
      non-remission acute myelogenous leukemia.
    

Eligibility 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