Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy and Total-Body Irradiation Followed by Peripheral Stem Cell or Bone Marrow Transplantation in Treating Patients With Acute Lymphoblastic Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 75 and under NCI FHCRC-1586.00 NCI-H01-0080, NCT00027547

Objectives

1. 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.
2. Evaluate the efficacy and toxicity of donor lymphocyte infusion in the treatment of minimal residual disease after nonmyeloablative allografting in these patients.

Entry 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

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

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

Expected Enrollment

A total of 30 patients (20 adults and 10 children) will be accrued for this study within 2 years.

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.

Trial Contact Information

Trial Lead Organizations

Fred Hutchinson Cancer Research Center

George Georges, MD, Protocol chair		Ph: 206-667-6886 Email: ggeorges@fhcrc.org

Registry Information
Official Title		Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation From HLA Matched Sibling Donors For Treatment Of Patients With High Risk Acute Lymphocytic Leukemia In Complete Remission
Trial Start Date		2001-07-27
Registered in ClinicalTrials.gov		NCT00027547
Date Submitted to PDQ		2001-10-04
Information Last Verified		2004-07-16
NCI Grant/Contract Number		CA78902, CA15704

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