Total-Body Irradiation and Cyclophosphamide in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer and Other Diseases

Sponsor

Fred Hutchinson Cancer Center (Other)

Overall Status

Completed

CT.gov ID

NCT00317785

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Patients Per Site

Study Details

Study Description

Brief Summary

RATIONALE: Giving total-body irradiation and chemotherapy, such as cyclophosphamide, before a donor stem cell transplant helps stop the patient's immune system from rejecting the donor's stem cells and helps stop the growth of cancer or abnormal cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving immunosuppressive therapy before or after transplant may stop this from happening.

PURPOSE: This phase II trial is studying how well giving total-body irradiation together with cyclophosphamide works in treating patients who are undergoing donor stem cell transplant for hematologic cancer and other diseases.

Condition or Disease	Intervention/Treatment	Phase
Leukemia Lymphoma Myelodysplastic Syndromes	Drug: cyclophosphamide Drug: cyclosporine Drug: methotrexate Drug: mycophenolate mofetil Drug: sirolimus Drug: tacrolimus Other: pharmacological study Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation	Phase 2

Detailed Description

OBJECTIVES:

Primary

Evaluate the potential efficacy of targeting cyclophosphamide to a metabolic endpoint when given together with total-body irradiation, in terms of day 200 nonrelapse mortality, in patients with hematologic cancer and other diseases who are undergoing allogeneic hematopoietic stem cell transplantation.

Secondary

Determine the overall survival of patients treated with this regimen.
Determine the rate of relapse in patients treated with this regimen.
Determine the occurrence of sinusoidal obstruction syndrome in patients treated with this regimen.
Determine the occurrence of acute renal failure in these patients.
Determine the occurrence of respiratory failure in these patients.

OUTLINE:

Conditioning regimen: Patients undergo total-body irradiation twice daily on days -6 to -4. Patients also receive cyclophosphamide IV over 1 hour on day -3 and then IV at a metabolism-based dose* on day -2.

NOTE: *Patients undergo frequent blood sampling after completion of the first cyclophosphamide infusion for pharmacokinetic studies in order to determine the dose for the second cyclophosphamide infusion.

Allogeneic stem cell transplantation: Patients undergo allogeneic bone marrow or peripheral blood stem cell transplantation on day 0.
Graft-versus-host disease (GVHD) prophylaxis: Patients receive GVHD prophylaxis as per the attending physician, including one of the following regimens: cyclosporine and methotrexate; tacrolimus and methotrexate; tacrolimus and mycophenolate mofetil; or sirolimus, tacrolimus, and methotrexate (as per the GVHD prophylaxis regimen chosen for each patient).

After completion of study treatment, patients are followed periodically for at least 200 days.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Trial of Total Body Irradiation Plus Metabolism-Based Cyclophosphamide Dosing as Preparative Therapy for Allogeneic Hematopoietic Cell Transplant for Patients With Hematological Malignancy

Study Start Date :

May 1, 2005

Actual Primary Completion Date :

Nov 1, 2007

Outcome Measures

Primary Outcome Measures

Non-relapse mortality (NRM) at 200 days []

Secondary Outcome Measures

Overall survival []
Relapse rate []
Sinusoidal obstruction syndrome (SOS) []
Acute renal failure []
Respiratory failure []
Cause of death []

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of a hematologic cancer or other disease that is unlikely to respond to conventional treatment, including any of the following:
Chronic myelogenous leukemia
Acute myeloid leukemia
Acute lymphocytic leukemia
Myelodysplastic syndromes
Lymphoma
Patients who have bulky tumor mass must not require additional involved-field irradiation
Planning to undergo conditioning for transplantation at the Seattle Cancer Care Alliance and University of Washington Medical Center
Must have an HLA-matched donor available
No donors who are mismatched for > 1 HLA class I antigen or allele
Negative anti-donor lymphocytotoxic crossmatch

PATIENT CHARACTERISTICS:

Life expectancy must not be severely limited by diseases other than malignancy
No moribund patients
Creatinine ≤ 1.2 mg/dL
Oxygen saturation on room air ≥ 93%
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No HIV positivity
No cirrhosis
No hepatic fibrosis with bridging
No fulminant hepatic failure
No acute liver injury
No persistent cholestasis
No infection requiring systemic antibiotic or antifungal therapy
No coronary artery disease
No congestive heart failure requiring therapy

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior hematopoietic stem cell transplantation
No prior radiation therapy to the liver or adjacent organs
More than 30 days since prior cytoreductive chemotherapy for patients with a large body burden of tumor cells
No concurrent enrollment in a phase I study