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
18 Years
70 Years
Both
Leukemia, Lymphoma, Myelodysplastic Syndromes
Trial Information
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
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Non-relapse mortality (NRM) at 200 days
Safety Issue:
No
Principal Investigator
George B. McDonald, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fred Hutchinson Cancer Research Center
Authority:
United States: Federal Government
Study ID:
1998.00
NCT ID:
NCT00317785
Start Date:
May 2005
Completion Date:
Related Keywords:
- Leukemia
- Lymphoma
- Myelodysplastic Syndromes
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- accelerated phase chronic myelogenous leukemia
- adult acute lymphoblastic leukemia in remission
- adult acute myeloid leukemia in remission
- blastic phase chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- de novo myelodysplastic syndromes
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- nodal marginal zone B-cell lymphoma
- noncontiguous stage II adult Burkitt lymphoma
- noncontiguous stage II adult diffuse large cell lymphoma
- noncontiguous stage II adult diffuse mixed cell lymphoma
- noncontiguous stage II adult diffuse small cleaved cell lymphoma
- noncontiguous stage II adult immunoblastic large cell lymphoma
- noncontiguous stage II adult lymphoblastic lymphoma
- noncontiguous stage II grade 1 follicular lymphoma
- noncontiguous stage II grade 2 follicular lymphoma
- noncontiguous stage II grade 3 follicular lymphoma
- noncontiguous stage II mantle cell lymphoma
- noncontiguous stage II marginal zone lymphoma
- noncontiguous stage II small lymphocytic lymphoma
- previously treated myelodysplastic syndromes
- recurrent adult acute lymphoblastic leukemia
- recurrent adult acute myeloid leukemia
- recurrent adult Burkitt lymphoma
- recurrent adult Hodgkin lymphoma
- recurrent adult diffuse large cell lymphoma
- recurrent adult diffuse mixed cell lymphoma
- recurrent adult diffuse small cleaved cell lymphoma
- recurrent adult immunoblastic large cell lymphoma
- recurrent adult lymphoblastic lymphoma
- recurrent cutaneous T-cell non-Hodgkin lymphoma
- recurrent grade 1 follicular lymphoma
- recurrent grade 2 follicular lymphoma
- recurrent grade 3 follicular lymphoma
- recurrent mantle cell lymphoma
- recurrent marginal zone lymphoma
- recurrent mycosis fungoides/Sezary syndrome
- recurrent small lymphocytic lymphoma
- relapsing chronic myelogenous leukemia
- secondary acute myeloid leukemia
- secondary myelodysplastic syndromes
- splenic marginal zone lymphoma
- stage III adult Burkitt lymphoma
- stage III adult Hodgkin lymphoma
- stage III adult diffuse large cell lymphoma
- stage III adult diffuse mixed cell lymphoma
- stage III adult diffuse small cleaved cell lymphoma
- stage III adult immunoblastic large cell lymphoma
- stage III adult lymphoblastic lymphoma
- stage III grade 1 follicular lymphoma
- stage III grade 2 follicular lymphoma
- stage III grade 3 follicular lymphoma
- stage III mantle cell lymphoma
- stage III marginal zone lymphoma
- stage III small lymphocytic lymphoma
- stage IV adult Burkitt lymphoma
- stage IV adult Hodgkin lymphoma
- stage IV adult diffuse large cell lymphoma
- stage IV adult diffuse mixed cell lymphoma
- stage IV adult diffuse small cleaved cell lymphoma
- stage IV adult immunoblastic large cell lymphoma
- stage IV adult lymphoblastic lymphoma
- stage IV grade 1 follicular lymphoma
- stage IV grade 2 follicular lymphoma
- stage IV grade 3 follicular lymphoma
- stage IV mantle cell lymphoma
- stage IV marginal zone lymphoma
- stage IV small lymphocytic lymphoma
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Myelodysplastic Syndromes
- Preleukemia
- Lymphoma, Large-Cell, Immunoblastic
Name | Location |
|---|---|
| Fred Hutchinson Cancer Research Center | Seattle, Washington 98109 |
| Seattle Cancer Care Alliance | Seattle, Washington 98109 |
