Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission
N/A
75 Years
Both
Leukemia
Trial Information
Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission
OBJECTIVES:
- Determine if a one-year disease free survival of 40% and a day 200 transplant-related
mortality of less than 25% can be achieved in patients with high-risk acute
lymphoblastic leukemia in complete remission treated with a nonmyeloablative
conditioning regimen comprising fludarabine and total body irradiation followed by
allogeneic peripheral blood stem cell or bone marrow transplantation.
- Evaluate the efficacy and toxicity of donor lymphocyte infusion in the treatment of
minimal residual disease after nonmyeloablative allografting in these patients.
OUTLINE: This is a multicenter study.
Patients receive a nonmyeloablative conditioning regimen comprising fludarabine IV on days
-4 to -2 and total body irradiation (TBI) on day 0. Children undergo allogeneic peripheral
blood stem cell transplantation (PBSCT) or bone marrow transplantation after TBI on day 0.
Adults undergo filgrastim (G-CSF)-mobilized allogeneic PBSCT after TBI on day 0.
Patients also receive graft-versus-host disease (GVHD) prophylaxis therapy comprising oral
cyclosporine twice daily on days -3 to 56 and then tapered and oral mycophenolate mofetil
once at 5-10 hours after transplantation on day 0 and then twice daily on days 1-27.
Patients who have no evidence of grade 2 or greater acute GVHD or clinically extensive
chronic GVHD, have been off GVHD prophylaxis therapy for 1-2 weeks, and have stable or
increasing minimal residual disease after discontinuation of GVHD prophylaxis therapy
receive donor lymphocyte infusion (DLI) IV over 30 minutes. DLI repeats every 4 weeks for a
total of 3 doses (if necessary).
Patients without a history of CNS leukemia and patients with a history of CNS leukemia
previously treated with prophylactic craniospinal irradiation receive methotrexate (MTX) or
cytarabine (ARA-C) intrathecally (IT) for a total of 2 doses before transplantation and for
a total of 6 doses beginning on day 32 after transplantation. Patients with a history of CNS
leukemia not previously treated with craniospinal irradiation undergo craniospinal
irradiation for 11 days before conditioning regimen and then MTX or ARA-C IT for a total of
6 doses beginning on day 32 after transplantation. Male patients also undergo testicular
radiotherapy for 7 days.
Patients are followed at 1, 2, 3, 6, 12, 18, and 24 months.
PROJECTED ACCRUAL: A total of 30 patients (20 adults and 10 children) will be accrued for
this study within 2 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of acute lymphoblastic leukemia (ALL)
- Adult patients must meet 1 of the following criteria:
- Age 50 to 75 with high-risk ALL in complete remission (CR) (less than 5% blasts
by morphology on bone marrow aspirate and absence of peripheral blasts) or ALL
in second CR (CR2) or greater
- Age 18 to 50 with high-risk ALL in first CR (CR1) and either ineligible for
conventional allogeneic transplantation (based on general medical condition) or
refused conventional transplantation
- High-risk adult ALL in CR1 includes patients meeting 1 or more of the
following criteria:
- Age 30 and over
- 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
- Age 18 to 50 with ALL in CR2 or greater and ineligible for conventional
allogeneic transplantation based on general medical condition
- Age 18 to 50 with high-risk ALL in CR2 or greater and refused conventional
allogeneic transplantation
- Pediatric patients must meet 1 of the following criteria:
- Under age 18 with high-risk ALL in CR1 and ineligible for conventional
allogeneic transplantation based on general medical condition
- High-risk pediatric ALL in CR1 includes patients meeting 1 or more of the
following criteria:
- Cytogenetic abnormalities
- t(9;22) with WBC at least 25,000/mm3 at diagnosis
- t(4;11) in patients under age 1 or age 10 and over
- Hypodiploidy (no more than 45 chromosomes)
- Failure to achieve CR after 4 weeks of induction chemotherapy
- Persistent peripheral blasts after 1 week of induction chemotherapy
- Under age 18 with CR2 or greater and ineligible for conventional allogeneic
transplantation based on general medical condition
- Age 12 and under allowed if approved by the principle investigator
- No active CNS disease
- Availability of a sibling donor (excluding an identical twin)
- HLA genotypically identical for at least 1 haplotype
- HLA-A, -B, -C, -DRB1, and -DQB1 genotypically or phenotypically identical
PATIENT CHARACTERISTICS:
Age:
- See Disease Characteristics
- 75 and under
Performance status:
- Karnofsky 50-100% (adults)
- Lansky 40-100% (children)
Life expectancy:
- Not specified
Hematopoietic:
- See Disease Characteristics
Hepatic:
- No fulminant liver failure
- No alcoholic hepatitis
- No history of bleeding esophageal varices
- No grade II or greater hepatic encephalopathy
- No hepatic synthetic dysfunction evidenced by prolongation of PT with INR greater
than 2.5
- No intractable ascites related to portal hypertension
- No bacterial or fungal liver abscess
- No chronic viral hepatitis with bilirubin greater than 5 mg/dL
- No biliary obstruction with bilirubin greater than 5 mg/dL
- No concurrent symptomatic biliary disease
Renal:
- Not specified
Cardiovascular:
- Cardiac ejection fraction at least 30%
Pulmonary:
- No requirement for supplementary continuous oxygen
Other:
- HIV negative
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 1 year after study
participation
PRIOR CONCURRENT THERAPY:
Biologic therapy
- No concurrent posttransplantation growth factors during mycophenolate mofetil
administration
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- Not specified
Radiotherapy
- Not specified
Surgery
- Not specified
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Principal Investigator
George Georges, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Fred Hutchinson Cancer Research Center
Authority:
United States: Federal Government
Study ID:
1586.00
NCT ID:
NCT00027547
Start Date:
July 2001
Completion Date:
July 2004
Related Keywords:
- Leukemia
- adult acute lymphoblastic leukemia in remission
- childhood acute lymphoblastic leukemia in remission
- Leukemia
- Leukemia, Lymphoid
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
| Cancer Institute at Oregon Health and Science University | Portland, Oregon 97201-3098 |
