Clinical trial NCT00112567: Total-Body Irradiation, Thiotepa, and Fludarabine in Treating Young Patients Who Are Undergoing a Donor Stem Cell Transplant for Hematologic Cancer
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Leukemia
Myelodysplastic Syndromes
Keywords: 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
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-06-03
Enrollment: 20
Sex: ALL
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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 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

Primary outcomes:
measure: Safety
Secondary outcomes:
measure: Risk of severe graft-versus-host disease
measure: Kinetics of immune reconstitution
measure: Risk of life-threatening infections
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Ann E. Woolfrey, MD
role: PRINCIPAL_INVESTIGATOR
References: