Reduced Intensity Donor Stem Cell Transplant in Treating Patients With High Risk Acute Lymphocytic Leukemia in Complete Remission
Adult Acute Lymphoblastic Leukemia in Remission, Childhood Acute Lymphoblastic Leukemia in Remission, Recurrent Adult Acute Lymphoblastic Leukemia
About this trial
This is an interventional treatment trial for Adult Acute Lymphoblastic Leukemia in Remission
Eligibility Criteria
Inclusion Criteria: ADULT PATIENTS: Patients 50-75 years old with high risk ALL in first CR (CR1) or ALL in CR >= second CR (CR2) Patients >= 18 years old and < 50 years old with high risk ALL in CR1 who are not eligible for a conventional allogeneic transplantation based on general medical condition Patients >= 18 years old and < 50 years old with high risk ALL in CR1 who refuse a conventional allogeneic transplant Patients >= 18 years old and < 50 years old with ALL in CR >= CR2 who are not eligible for a conventional allogeneic transplantation based on general medical condition Patients >= 18 years old and < 50 years old with high risk ALL in CR >= CR2 who refuse a conventional allogeneic transplant CR is defined as < 5% blasts by morphology on a bone marrow aspirate and the absence of peripheral blasts High risk adult ALL in CR1 includes those patients with one or more of the following: Age >=30 years Non T-cell phenotype Cytogenetic abnormalities including t(9;22), t(4;11), trisomy 8, or monosomy 7 Failure to achieve CR after 4 weeks of induction chemotherapy PEDIATRIC PATIENTS: Patients < 18 years old with ALL in high risk CR1 who are not candidates for conventional allogeneic transplantation based on general medical condition Patients < 18 years old with ALL in CR >= CR2 who are not candidates for conventional allogeneic transplantation based on general medical condition Patients < 12 years old require approval by the Fred Hutchinson Cancer Research Center (FHCRC) principal investigator prior to enrollment CR is defined as < 5% blasts by morphology on a bone marrow aspirate and absence of peripheral blasts High risk pediatric ALL in CR1 includes those patients with one or more of the following: Cytogenetic abnormalities including: t(9;22) with a white blood cell (WBC) >= 25,000 at diagnosis or t(4;11) in patients < 1 year old and >= 10 years old or Hypodiploidy (< 45 chromosomes) Failure to achieve CR after 4 weeks of induction chemotherapy Persistent peripheral blasts after one week of induction chemotherapy DONOR: FHCRC matching Grade 2.1: Unrelated donors who are prospectively: Matched for human leukocyte antigen (HLA)-DRB1 and DQB1 alleles (must be defined by high resolution typing) and Only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing DONOR: A positive anti-donor cytotoxic crossmatch is an absolute donor exclusion; donors are excluded when preexisting immunoreactivity is identified that would jeopardize donor hematopoietic cell engraftment; this determination is based on the standard practice of the individual institution; the recommended procedure for patients with 10 of 10 HLA allele level (phenotypic) match is to obtain a panel reactive antibody (PRA) screens to class I and class II antigens for all patients before hematopoietic cell transplantation (HCT); if the PRA shows > 10% activity, then flow cytometric or B and T cell cytotoxic cross matches should be obtained; the donor should be excluded if any of the cytotoxic cross match assays are positive; for those patients with an HLA class I allele mismatch, flow cytometric or B and T cell cytotoxic cross matches should be obtained regardless of the PRA results DONOR: Patient and donor pairs homozygous at a mismatched allele are considered a two-allele mismatch, i.e., the patient is A*0101 and the donor is A*0102, and this type of mismatch is not allowed DONOR: Donor must consent to peripheral blood stem cell (PBSC) mobilization with filgrastim (G-CSF) arranged through the National Marrow Donor Program (NMDP) or other donor centers Exclusion Criteria: Active central nervous system (CNS) disease Presence of circulating leukemic blasts (in the peripheral blood) detected by standard pathology Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment Pregnancy or breastfeeding Human immunodeficiency virus (HIV) seropositivity ORGAN DYSFUNCTION, ADULT CRITERIA: Requiring supplementary continuous oxygen OR diffusing capacity of the lung for carbon monoxide (DLCO) < 40% Cardiac ejection fraction < 35% 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, 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, bridging fibrosis, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dL, and symptomatic biliary disease Karnofsky performance score < 50 ORGAN DYSFUNCTION, PEDIATRIC CRITERIA: Lansky play-performance score < 40 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
Sites / Locations
- Oregon Health and Sciences University
- Veterans Affairs Puget Sound Healthcare System
- Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Arms of the Study
Arm 1
Experimental
Treatment (nonmyeloablative allogeneic PBSCT)
NONMYELOALATIVE CONDITIONING REGIMEN: Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI on day 0. TRANSPLANTATION: Patients undergo allogeneic PBSCT on day 0. Patients with minimal residual disease may receive donor lymphocyte infusion IV. IMMUNOSUPPRESSION: Patients receive cyclosporine PO every 12 hours on days -3 to 100 with taper to day 177 and mycophenolate mofetil PO very 8 hours on days 0 to 40 with taper to day 96.