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

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00112567

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Duration (Months)

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Myelodysplastic Syndromes	Drug: fludarabine phosphate Drug: thiotepa Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy	Phase 1/Phase 2

Detailed 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

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/II Study of Total Body Irradiation, Thiotepa, and Fludarabine as Conditioning for Haploidentical CD34+ Purified Peripheral Blood Stem Cell Transplants

Study Start Date :

Apr 1, 2003

Study Completion Date :

Jul 1, 2007

Outcome Measures

Primary Outcome Measures

Safety []

Secondary Outcome Measures

Risk of severe graft-versus-host disease []
Kinetics of immune reconstitution []
Risk of life-threatening infections []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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