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

Alternate Title

Donor Peripheral Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Closed 75 and under NCI FHCRC-1623.00 NCI-H02-0085, NCT00031655

Objectives

Primary

1. Determine the 1-year disease-free survival of patients with acute lymphoblastic leukemia in complete remission treated with nonmyeloablative allogeneic peripheral blood stem cell transplantation from HLA-matched unrelated donors.

Secondary

1. Determine the day 200 transplant-related mortality in patients treated with this regimen.
2. Determine the efficacy of donor lymphocyte infusions (DLI) in patients treated with this regimen.
3. Determine the toxicity of DLI in patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Diagnosis of adult or pediatric acute lymphoblastic leukemia (ALL)
  • Age 50 to 75 with high-risk disease in complete remission (CR)1 OR disease in CR2 or greater
  • Age 18 to 49 with high-risk disease in CR1 OR disease in CR2 or greater and ineligible for or refused conventional allogeneic transplantation
    • CR is defined as:
      • Less than 5% blasts by morphology on a bone marrow biopsy and absence of peripheral blasts
    • High-risk adult ALL in CR1 defined as 1 or more of the following:
      • 30 years of age or over
      • Non-T-cell phenotype
      • Cytogenetic abnormalities (e.g., t(9;22), t(4;11), trisomy 8, or monosomy 7)
      • Failure to achieve CR after 4 weeks of induction chemotherapy
  • Under 18 years of age with high-risk disease in CR1 OR disease in CR2 or greater and ineligible for conventional allogeneic transplantation
    • High-risk pediatric ALL in CR1 defined as 1 or more of the following:
      • Cytogenic abnormalities (e.g., t(9;22) with WBC ≥ 25,000/mm3 at diagnosis, t(4;11) if under 1 year of age or 10 years of age and over, hypodiploidy [< 45 chromosomes])
      • Failure to achieve CR after 4 weeks of induction chemotherapy
      • Persistent peripheral blasts after 1 week of induction chemotherapy



• No active CNS disease



• Must have unrelated donor matched for HLA-DRB1 and -DQB1 by high-resolution typing
  • Single allele disparity allowed for HLA-A, -B, or -C
  • Anti-donor cytotoxic crossmatch negative
  • Patients and donor pairs homozygous at a mismatched allele are considered a 2 allele mismatch (i.e., patient A*0101 and donor A*0102) and therefore not eligible

Prior/Concurrent Therapy:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics

Endocrine:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Patient Characteristics:

Age:

• See Disease Characteristics
• 75 and under

Performance status:

• Karnofsky 50-100% (17 years of age and over)
• Lansky 40-100% (under 17 years of age)

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• No fulminant liver failure
• No cirrhosis of the liver with evidence of portal hypertension
• No alcoholic hepatitis
• No esophageal varices
• No history of bleeding esophageal varices
• No hepatic encephalopathy
• No uncontrolled hepatic synthetic dysfunction as evidenced by prolongation of PT
• No ascites related to portal hypertension
• No bridging fibrosis
• No bacterial or fungal liver abscess
• No biliary obstruction
• No chronic viral hepatitis AND bilirubin > 3 mg/dL
• No symptomatic biliary disease

Renal:

• Not specified

Cardiovascular:

• Cardiac ejection fraction ≥ 35%*

   [Note: *Adults only]

Pulmonary:

• No requirement for supplementary continuous oxygen*

  OR

• DLCO ≥ 40% of predicted*

   [Note: *Adults only]

Other:

• HIV negative
• Not pregnant or nursing
• Fertile patients must use effective contraception during and for 12 months after study participation
• No active nonhematologic malignancy within the past 5 years except nonmelanoma skin cancer
  • Previous nonhematologic malignancies must have ≤ 20% risk of disease recurrence

Expected Enrollment

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

Outcomes

Disease-free survival (DFS) > 25% among adult patients at 1 year
DFS > 40% among pediatric patients at 1 year

Outline

This is a multicenter study.

Patients receive fludarabine IV on days -4 to -2. Patients undergo total body irradiation on day 0 followed by allogeneic peripheral blood stem cell infusion. Patients also receive oral cyclosporine twice daily on days -3 to 100 with a taper from day 101-177 and oral mycophenolate mofetil 3 times daily on days 0-40 with a taper from day 41-96.

Beginning 1-2 weeks after withdrawal of immunosuppression, patients with no evidence of acute graft-vs-host disease grade 2 or greater and no morphological disease progression may receive up to 3 donor lymphocyte infusions (DLI) IV over 30 minutes.

Patients are followed monthly for 4 months, at 6, 12, 18, and 24 months, and then annually for 3 years.

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 Unrelated Donors for Treatment of Patients with High Risk Acute Lymphocytic Leukemia in Complete Remission
Trial Start Date		2001-09-28
Registered in ClinicalTrials.gov		NCT00031655
Date Submitted to PDQ		2002-01-02
Information Last Verified		2006-04-08
NCI Grant/Contract Number		CA78902, CA15704, CA18029, CA09515

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