Total-Body Irradiation, Thiotepa, and Fludarabine in Treating Young Patients Who Are Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

Fred Hutchinson Cancer Center (FHCC)

Status and phase: Completed; Phase 2; Phase 1

Conditions: Leukemia; Myelodysplastic Syndromes

Treatments: Procedure: peripheral blood stem cell transplantation; Drug: thiotepa; Drug: fludarabine phosphate; Radiation: radiation therapy

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00112567

1629.00

FHCRC-1629.00

CDR0000430650 (Registry Identifier)

Details and patient eligibility

About

RATIONALE: Chemotherapy, such as fludarabine and thiotepa, and radiation therapy may destroy cancerous blood-forming cells (stem cells) in the blood and bone marrow. Giving healthy stem cells from a donor whose blood closely resembles the patient's blood will help the patient's bone marrow make new stem cells that become red blood cells, white blood cells, and platelets.

PURPOSE: This phase I/II trial is studying the side effects of total-body irradiation, fludarabine, and thiotepa and to see how well they work in treating young patients who are undergoing a donor stem cell transplant for hematologic cancer.

Full description

OBJECTIVES:

Primary

• Determine the safety of a conditioning regimen without anti-thymocyte globulin comprising total body irradiation, thiotepa, and fludarabine followed by CD34-positive-selected haploidentical allogeneic peripheral blood stem cell transplantation in young patients with life-threatening hematologic malignancies.

Secondary

• Determine the risk for severe graft-vs-host disease in patients treated with this regimen.
• Determine the kinetics of immune reconstitution in patients treated with this regimen.
• Determine the risk for life-threatening infections in patients treated with this regimen.

OUTLINE:

• Conditioning regimen: Patients 7 years of age and under undergo total body irradiation twice daily on days -9 to -7. Patients over 7 years of age undergo total body irradiation once on day -7. All patients receive fludarabine IV once daily on days -6 to -2 and thiotepa IV over 2 hours twice on day -5.
• CD34-positive (CD34+)-selected haploidentical allogeneic peripheral blood stem cell transplantation (PBSCT): Patients undergo CD34+-selected allogeneic PBSCT on days 0 and 2.

Patients with acute lymphoblastic leukemia or CNS disease also receive methotrexate intrathecally twice before transplantation and 4 times after day 35 post-transplantation. Male patients with lymphoid malignancies undergo additional radiotherapy to the testes.

After completion of study treatment, patients are followed for at least 100 days, at 1 year, and then periodically thereafter.

PROJECTED ACCRUAL: A total of 20 patients (10 patients ≤ 7 years of age and 10 patients > 7 years of age) will be accrued for this study within 3 years.

Enrollment: 20 estimated patients

Sex: All

Ages: Under 20 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

• Diagnosis of a life-threatening hematologic malignancy, including any of the following:

  • Acute leukemia advanced beyond first remission

  • Acute leukemia in first remission* with very high-risk prognostic features, including any of the following:

    • Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL)
    • ALL or acute myeloid leukemia (AML) with 11q23 chromosomal abnormality
    • Hypodiploid ALL
    • Failed to achieve first remission within 1 month after induction therapy
    • Secondary AML

  • Myelodysplastic syndromes with International Prognostic Index score > 1

  • Chronic myelogenous leukemia in accelerated or blast phase NOTE: *Must be approved by PCC

• Haploidentical family donor available

  • No suitable HLA-matched related or unrelated donor available
  • No related donor mismatched for a single HLA-A, -B, -C, -DRB1, or -DQB1 antigen available

PATIENT CHARACTERISTICS:

Age

• Under 21

Performance status

• Not specified

Life expectancy

• At least 6 months

Hematopoietic

• Not specified

Hepatic

• SGPT and SGOT < 2 times upper limit of normal (ULN)*
• Bilirubin < 2 times ULN* NOTE: *Unless due to malignancy

Renal

• Not specified

Cardiovascular

• Ejection fraction ≥ 45%

Pulmonary

• DLCO ≥ 60% of predicted

Other

• Not pregnant or nursing
• Fertile patients must use effective contraception
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No second bone marrow transplantation, after a first regimen containing total body irradiation
• No concurrent growth factors until day 21 post-transplantation

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• See Biologic therapy

Surgery

• Not specified