Blood Stem Cell Transplantation for the Treatment of Older Patients With Acute Myelogenous Leukemia - Full Text View

Sponsored by:	University of Michigan Cancer Center
Information provided by:	University of Michigan Cancer Center
ClinicalTrials.gov Identifier:	NCT00623935

Purpose

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.

Condition	Intervention	Phase
Acute Myelogenous Leukemia	Drug: Fludarabine, Busulfan (FluBu2) Drug: Fludarabine, Busulfan (FluBu4) Radiation: total body irradiation Procedure: stem cell transplant	Phase II

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Fludarabine Fludarabine monophosphate Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
Official Title:	Hematopoietic Stem Cell Transplantation for the Treatment of Older Patients With Acute Myelogenous Leukemia

Further study details as provided by University of Michigan Cancer Center:

Primary Outcome Measures:

To determine the 1 year relapse free survival (RFS) for individuals > 55 years in age with AML in CR1 who undergo a 7-8/8 HLA- matched unrelated donor transplant using a reduced intensity regimen. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To determine the risk of transplant related mortality, acute and chronic GVHD, RFS (at 1 year) and overall survival for patients > 55 years in age with AML undergoing full or reduced transplant with the best available donor. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	March 2007
Estimated Study Completion Date:	March 2011
Estimated Primary Completion Date:	March 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
CR: Experimental Patients in CR will receive a reduced intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu2).	Drug: Fludarabine, Busulfan (FluBu2) Fludarabine (40 mg/m2/day x 4 days) plus Busulfan (3.2 mg/m2/day x 2 days) Radiation: total body irradiation Patients on the FluBu2 arm who receive a mismatched allograft (7/8 HLA match) will additionally receive 200 cGy of total body irradiation (TBI) pre-transplant. Procedure: stem cell transplant Allogeneic stem cell transplant from related or unrelated donor
PR: Experimental Patients in PR will receive a full intensity transplant regimen consisting of Fludarabine plus Busulfan (FluBu4).	Drug: Fludarabine, Busulfan (FluBu4) Fludarabine (40 mg/m2/day x 4 days) plus Busulfan (3.2 mg/m2/day x 4 days). Procedure: stem cell transplant Allogeneic stem cell transplant from related or unrelated donor

Arms

Assigned Interventions

CR: Experimental

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

Drug: Fludarabine, Busulfan (FluBu2)

Fludarabine (40 mg/m2/day x 4 days) plus Busulfan (3.2 mg/m2/day x 2 days)

Radiation: total body irradiation

Patients on the FluBu2 arm who receive a mismatched allograft (7/8 HLA match) will additionally receive 200 cGy of total body irradiation (TBI) pre-transplant.

Procedure: stem cell transplant

Allogeneic stem cell transplant from related or unrelated donor

PR: Experimental

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

Drug: Fludarabine, Busulfan (FluBu4)

Fludarabine (40 mg/m2/day x 4 days) plus Busulfan (3.2 mg/m2/day x 4 days).

Procedure: stem cell transplant

Allogeneic stem cell transplant from related or unrelated donor

Eligibility

Ages Eligible for Study:	55 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

For Study Registration:

Age 55 - 70 years.
Subjects diagnosed with AML (> 20% myeloblasts).

For Proceeding to Tranplant:

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
- Karnfosky > 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.
- Karnfosky > 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00623935

Contacts

Contact: Gregory Yanik, MD

734-936-8785

gyanik@med.umich.edu

Locations

United States, Michigan
University of Michigan Cancer Center	Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Gregory Yanik, MD 734-936-8785 gyanik@med.umich.edu
Principal Investigator: Gregory Yanik, MD

Sponsors and Collaborators

University of Michigan Cancer Center

Investigators

Principal Investigator:

Gregory Yanik, MD

University of Michigan Comprehesive Cancer Ctr

More Information

Responsible Party:	University of Michigan Health System ( Gregory Yanik M.D / Department of Pediatrics-Hematology/Oncology )
Study ID Numbers:	UMCC 2006.065, HUM00006772
Study First Received:	February 14, 2008
Last Updated:	August 6, 2008
ClinicalTrials.gov Identifier:	NCT00623935
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Michigan Cancer Center:

AML

Study placed in the following topic categories:

Leukemia
Busulfan
Acute myelogenous leukemia
Fludarabine

Fludarabine monophosphate
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Acute myelocytic leukemia

Additional relevant MeSH terms:

Antimetabolites
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs

Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Therapeutic Uses
Myeloablative Agonists
Antineoplastic Agents, Alkylating
Alkylating Agents

ClinicalTrials.gov processed this record on January 16, 2009