Brief Title
Reduced Intensity Donor Peripheral Blood Stem Cell Transplant in Treating Patients With De Novo or Secondary Acute Myeloid Leukemia in Remission
Official Title
Nonmyeloablative Allogeneic Peripheral Blood Stem Cell Transplantation From HLA Matched Related Donors for Treatment of Older Patients With De Novo or Secondary Acute Myeloid Leukemia in First Complete Remission
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Disease-free Survival-incidence of Survival Without Relapse
Secondary Outcome
Overall Survival
Condition
Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome
Intervention
nonmyeloablative allogeneic hematopoietic stem cell transplantation
Study Arms / Comparison Groups
Treatment (nonmyeloablative donor PBSC transplant)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Procedure
Estimated Enrollment
17
Start Date
April 2002
Completion Date
January 2009
Primary Completion Date
January 2009
Eligibility Criteria
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
Gender
All
Ages
55 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Brenda Sandmaier, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00045435
Organization ID
1654.00
Secondary IDs
NCI-2011-01307
Responsible Party
Principal Investigator
Study Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Brenda Sandmaier, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
January 2020