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

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00112567
First received: June 2, 2005
Last updated: September 17, 2010
Last verified: September 2010
History of Changes
  Purpose

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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Risk of severe graft-versus-host disease [ Designated as safety issue: No ]
  • Kinetics of immune reconstitution [ Designated as safety issue: No ]
  • Risk of life-threatening infections [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: April 2003
Estimated Study Completion Date: July 2007
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 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.

  Eligibility

Ages Eligible for Study:   up to 20 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00112567

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98104
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ann E. Woolfrey, MD Fred Hutchinson Cancer Research Center
  More Information

Additional Information:
Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

No publications provided

ClinicalTrials.gov Identifier: NCT00112567     History of Changes
Other Study ID Numbers: 1629.00, FHCRC-1629.00, CDR0000430650
Study First Received: June 2, 2005
Last Updated: September 17, 2010
Health Authority: United States: Federal Government

Keywords provided by Fred Hutchinson Cancer Research Center:
recurrent childhood acute lymphoblastic leukemia
childhood myelodysplastic syndromes
childhood acute lymphoblastic leukemia in remission
recurrent childhood acute myeloid leukemia
childhood acute myeloid leukemia in remission
secondary acute myeloid leukemia
accelerated phase chronic myelogenous leukemia
 blastic phase chronic myelogenous leukemia
childhood chronic myelogenous leukemia
relapsing chronic myelogenous leukemia
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
previously treated myelodysplastic syndromes

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Thiotepa
Fludarabine
Fludarabine monophosphate
Vidarabine
Antineoplastic Agents, Alkylating
 Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on May 19, 2013