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

University of Michigan Rogel Cancer Center

Status and phase: Completed; Phase 2

Conditions: Acute Myelogenous Leukemia

Treatments: Drug: Busulfan; Procedure: Stem Cell Transplant; Drug: Fludarabine; Radiation: Total Body Irradiation

Study type: Interventional

Funder types: Other

Identifiers

NCT00623935

HUM00006772 (Other Identifier)

UMCC 2006.065

Details and patient eligibility

About

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.

Enrollment: 56 patients

Sex: All

Ages: 55 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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56 participants in 2 patient groups

Fludarabine plus Busulfan (CR)

Experimental group

Description:

Patients in CR will receive a reduced intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu2).

Treatment:

Drug: Fludarabine

Radiation: Total Body Irradiation

Procedure: Stem Cell Transplant

Drug: Busulfan

Fludarabine plus Busulfan (PR)

Experimental group

Description:

Patients in PR will receive a full intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu4).

Treatment:

Drug: Fludarabine

Procedure: Stem Cell Transplant

Drug: Busulfan