Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission

Phase 2

Completed

Conditions: Adult Acute Myeloid Leukemia in Remission
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Del(5q)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Secondary Acute Myeloid Leukemia
Adult Acute Myeloblastic Leukemia Without Maturation (M1)

Interventions: Procedure: nonmyeloablative allogeneic hematopoietic stem cell transplantation
Drug: fludarabine phosphate
Radiation: total-body irradiation
Drug: cyclosporine
Drug: mycophenolate mofetil
Procedure: peripheral blood stem cell transplantation

Registration Number: NCT00045435

Lead Sponsor: Fred Hutchinson Cancer Center

Brief Summary: This phase II trial studies how well reduced intensity donor peripheral blood stem cell (PBSC) transplant works in treating patients with de novo or secondary acute myeloid leukemia (AML) in remission. Giving low doses of chemotherapy, such as fludarabine phosphate, and total-body irradiation (TBI) before a donor PBSC transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and mycophenolate mofetil after the transplant may stop this from happening

Detailed Description: PRIMARY OBJECTIVES:

I. To determine if a one-year disease free survival of \>= 35% can be achieved among patients \>= 55 years old with de novo and secondary AML in first complete remission (CR1) who undergo nonmyeloablative hematopoietic stem cell transplant (HSCT) from human leukocyte antigen (HLA) identical related donors.

II. To determine if a day +200 nonrelapse related mortality of \< 15% can be achieved among patients \>= 55 years old with de novo and secondary AML in CR1 who undergo nonmyeloablative HSCT from HLA identical related donors.

OUTLINE:

CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -4 to -2 and undergo TBI on day 0.

TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0.

IMMUNOSUPPRESSION: Patients receive cyclosporine (CSP) orally (PO) twice daily (BID) on days -3 to 56 with taper to day 77. Patients also receive mycophenolate mofetil (MMF) PO BID on days 0-27.

After completion of study treatment, patients are followed up on days 28, 56, and 84; months 6, 12, 18, and 24; and then yearly for 5 years.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 17

Inclusion Criteria

Patients with de novo AML (French-American-British [FAB] MO-M2, M4-M7) or secondary AML who achieve CR1 after induction chemotherapy and one or two cycles of consolidation chemotherapy
Transplant conditioning must occur within 6 months of diagnosis
Patient enrollment must be approved by the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator (PI) or the PI's designee
DONOR: Related donor who is genotypically or phenotypically identical
DONOR: Age >= 12 years
DONOR: Donor must consent to filgrastim (G-CSF) administration and leukapheresis
DONOR: Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

Exclusion Criteria

AML FAB M3
AML involvement of the central nervous system (CNS) as defined by a positive cytospin of cerebral spinal fluid at the time of enrollment
Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology
Human immunodeficiency virus (HIV) seropositivity
Fungal infections with radiographic progression after receipt of amphotericin B or active triazole for greater than one month
Diffusion capacity of carbon monoxide (DLCO) corrected < 40%
Total lung capacity (TLC) < 40%
Forced expiratory volume in one second (FEV1) < 40% or requiring supplementary oxygen
The FHCRC principal investigator of the study must approve enrollment of all patients with pulmonary nodules
Cardiac ejection fraction < 40%
Patients with clinical or laboratory evidence of liver disease would be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3mg/dL, or symptomatic biliary disease
Karnofsky Performance Score < 70
Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
Females who are pregnant or breastfeeding
No intensive chemotherapy can be given within three weeks (or the interval in which a cycle of standard chemotherapy would be administered in a non-transplant setting) prior to initiating the nonmyeloablative transplant conditioning
Patients with active non-hematologic malignancies (except non-melanoma skin cancers)
Patients with a history of non-hematologic malignancies (except non-melanoma skin cancers) currently in a complete remission, who are less than 5 years from the time of complete remission, and have a > 20% risk of disease recurrence
Patients with active bacterial or fungal infections unresponsive to medical therapy
DONOR: Identical twin
DONOR: Pregnancy
DONOR: HIV seropositivity
DONOR: Inability to achieve adequate venous access
DONOR: Known allergy to G-CSF
DONOR: Current serious systemic illness

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (nonmyeloablative donor PBSC transplant)	nonmyeloablative allogeneic hematopoietic stem cell transplantation	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Treatment (nonmyeloablative donor PBSC transplant)	total-body irradiation	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Treatment (nonmyeloablative donor PBSC transplant)	mycophenolate mofetil	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Treatment (nonmyeloablative donor PBSC transplant)	peripheral blood stem cell transplantation	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Treatment (nonmyeloablative donor PBSC transplant)	fludarabine phosphate	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.
Treatment (nonmyeloablative donor PBSC transplant)	cyclosporine	CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANT: Patients undergo allogeneic PBSC transplant on day 0. IMMUNOSUPPRESSION: Patients receive CSP PO BID on days -3 to 56 with taper to day 77. Patients also receive MMF PO BID on days 0-27.

Primary Outcome Measures

Name	Time	Method
Disease-free Survival-incidence of Survival Without Relapse	By 1 year after transplant	Sufficient evidence will be taken to be an observed rate of DFS at one year after transplant that corresponds to a one-sided 95% confidence interval with an upper limit lower than 35%.
Nonrelapse Mortality (NRM)-Incidence of Nonrelapse Death	200 days after transplant	Defined as death without morphologic evidence of disease. Sufficient evidence will be taken to be an observed rate of NRM within 200 days of transplant that corresponds to a one-sided 80% confidence interval with a lower limit greater than 15%.

Secondary Outcome Measures

Name	Time	Method
Incidence of Rejection	By 1 year after transplant	Percent patients who developed infections post-transplant.
Overall Survival	By 1 year after transplant	Percent patients surviving.
Incidence of Relapse	By 1 year after transplant	Percent patients with relapsed disease post-transplant.
Incidence of Acute and Chronic GVHD	aGVHD: 100 days after transplant; cGVHD: 1 Year after transplant.	Percent patients with acute/chronic GVHD

Trial Locations

Locations (2): OHSU Cancer Institute
🇺🇸
Portland, Oregon, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
🇺🇸
Seattle, Washington, United States