Acute Myelogenous Leukemia
Conditions
Keywords
AML
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.
Interventions
DRUGFludarabine
Fludarabine (40 mg/m2/day x 4 days)
DRUGBusulfan
Busulfan (3.2 mg/m2/day x 2 days or x 4 days).
RADIATIONTotal Body Irradiation
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.
PROCEDUREStem Cell Transplant
Allogeneic stem cell transplant from related or unrelated donor
Sponsors
University of Michigan Rogel Cancer Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
55 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Fludarabine Plus Busulfan Patients will receive a reduced intensity transplant regimen consisting of Fludarabine (40 mg/m2/day x 4 days) plus Busulfan (3.2 mg/m2/day x 2 days or 3.2 mg/m2/day x 4 days)
Patients who receive Busulfan at 3.2mg/m2/day x 2 days, and a mismatched allograft (7/8 HLA match), will additionally receive 200 cGy of total body irradiation (TBI) pre-transplant.
Patients will undergo an allogeneic stem cell transplant from related or unrelated donor. | 56 |
| Total | 56 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | Patient Declined Transplant | 1 |
Baseline characteristics
| Characteristic | Fludarabine Plus Busulfan |
|---|---|
| Age, Continuous | 61 years |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 56 |
| serious Total, serious adverse events | 21 / 56 |
Outcome results
Primary
Percentage of Participants With Relapse Free Survival at 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.
Time frame: 1 year
Population: 56 patients were enrolled. 54 patients were treated (one died prior to transplant, one did not undergo a transplant) and 4 patients were inevaluable (3 patients were less than 1 year post transplant at the time the abstract was written and 1 failed to engraft).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine Plus Busulfan | Percentage of Participants With Relapse Free Survival at 1 Year | 56 percentage of participants |
Secondary
Percentage of Participants Alive at 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.
Time frame: 1 year
Population: 56 patients were enrolled. 54 patients were treated (one died prior to transplant, one did not undergo a transplant) and 4 patients were inevaluable (3 patients were less than 1 year post transplant at the time the abstract was written and 1 failed to engraft).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Fludarabine Plus Busulfan | Percentage of Participants Alive at 1 Year | 58 percentage of participants |