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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00112567
• Other study ID #: 1629.00
• Secondary ID: FHCRC-1629.00CDR
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 2, 2005
• Last updated: September 17, 2010
• Start date: April 2003
• Est. completion date: July 2007

Study information

• Verified date: September 2010
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 20 Years

Eligibility

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

Study Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• fludarabine phosphate

• thiotepa

Procedure:
• peripheral blood stem cell transplantation

Radiation:
• radiation therapy

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety			Yes
Secondary	Risk of severe graft-versus-host disease			No
Secondary	Kinetics of immune reconstitution			No
Secondary	Risk of life-threatening infections			No