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

Phase 2

Completed

• Conditions: Acute Myelogenous Leukemia
• Interventions: Drug: Fludarabine; Drug: Busulfan; Radiation: Total Body Irradiation; Procedure: Stem Cell Transplant

• Registration Number: NCT00623935
• Lead Sponsor: University of Michigan Rogel Cancer Center

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-03
• Study First Submitted: 2008-02-14
• Study First Submitted QC: 2008-02-25
• Study First Posted: 2008-02-26
• Primary Completion: 2013-06
• Results First Submitted: 2014-06-17
• Results First Submitted QC: 2014-06-17
• Results First Posted: 2014-07-17
• Study Completion: 2015-11
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-10
• Last Update Posted: 2016-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 56

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fludarabine plus Busulfan (CR)	Fludarabine	Patients in CR will receive a reduced intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu2).
Fludarabine plus Busulfan (CR)	Busulfan	Patients in CR will receive a reduced intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu2).
Fludarabine plus Busulfan (CR)	Total Body Irradiation	Patients in CR will receive a reduced intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu2).
Fludarabine plus Busulfan (CR)	Stem Cell Transplant	Patients in CR will receive a reduced intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu2).
Fludarabine plus Busulfan (PR)	Fludarabine	Patients in PR will receive a full intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu4).
Fludarabine plus Busulfan (PR)	Busulfan	Patients in PR will receive a full intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu4).
Fludarabine plus Busulfan (PR)	Stem Cell Transplant	Patients in PR will receive a full intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu4).

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Relapse Free Survival at 1 Year	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.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Alive at 1 Year	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.

Trial Locations

Locations (1)

University of Michigan Cancer Center; 🇺🇸 Ann Arbor, Michigan, United States