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Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission


Phase 1/Phase 2
N/A
75 Years
Not Enrolling
Both
Leukemia

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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 CenterSeattle, Washington  98109
Cancer Institute at Oregon Health and Science UniversityPortland, Oregon  97201-3098