Blood Stem Cell Transplantation for the Treatment of Older Patients With Acute Myelogenous Leukemia
Condition: Acute Myelogenous Leukemia
MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
Intervention: Fludarabine; Busulfan; Total Body Irradiation; Stem Cell Transplant
Intervention description: Fludarabine (40 mg/m2/day x 4 days); Busulfan (3.2 mg/m2/day x 2 days or x 4 days).; 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.; Allogeneic stem cell transplant from related or unrelated donor
Intervention MeSH terms: Fludarabine; Busulfan
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 56.0
Sex: All
Minimum age: 55 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: AML

Summary:

      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.
    

Eligibility criteria:

        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