Busulfan, Fludarabine, and Total-Body Irradiation in Treating Patients Who Are Undergoing a Donor Stem Cell Transplant for Hematologic Cancer
| Status: | Completed |
|---|---|
| Conditions: | Cancer, Cancer, Blood Cancer, Lymphoma, Hematology, Leukemia |
| Therapuetic Areas: | Hematology, Oncology |
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 10/14/2017 |
| Start Date: | June 2005 |
| End Date: | August 2015 |
A Phase I/II Non-Myeloablative Allogeneic Hematopoietic Stem Cell Transplant for the Treatment of Patients With Hematologic Malignancies Using Busulfan, Fludarabine and Total Body Irradiation
RATIONALE: Giving low doses of chemotherapy, such as fludarabine and busulfan, before a donor
peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops
the patient's immune system from rejecting the donor's stem cells. The donated stem cells may
replace the patient's immune system and help destroy any remaining cancer cells
(graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte
infusion) after the transplant may help increase this effect. Sometimes the transplanted
cells from a donor can also make an immune response against the body's normal cells. Giving
cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of giving busulfan and
fludarabine together with total-body irradiation and to see how well they work in treating
patients who are undergoing a donor stem cell transplant for hematologic cancer.
peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops
the patient's immune system from rejecting the donor's stem cells. The donated stem cells may
replace the patient's immune system and help destroy any remaining cancer cells
(graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte
infusion) after the transplant may help increase this effect. Sometimes the transplanted
cells from a donor can also make an immune response against the body's normal cells. Giving
cyclosporine and mycophenolate mofetil after the transplant may stop this from happening.
PURPOSE: This phase I/II trial is studying the side effects of giving busulfan and
fludarabine together with total-body irradiation and to see how well they work in treating
patients who are undergoing a donor stem cell transplant for hematologic cancer.
OBJECTIVES:
Primary
- To assess safety and toxicity of the addition of busulfan added to an established
fludarabine and low-dose total-body irradiation (TBI) conditioning regimen for
non-myeloablative allogeneic transplantation in patients with hematologic malignancies.
(Phase I)
- To assess the non-relapse mortality 1-year after conditioning with busulfan and
fludarabine/TBI in patients with hematologic malignancies at moderate to high risk for
graft rejection and/or relapse of underlying disease. (Phase II)
Secondary
- To assess overall survival 1-year survival. (Phase II)
- To assess the incidence of graft rejection. (Phase II)
- To assess the incidence of grade II-IV acute graft-vs-host disease (GVHD) and chronic
extensive GVHD. (Phase II)
- To assess rates of disease progression and/or relapse-related mortality. (Phase II)
- To determine non-hematologic grade III-IV organ specific toxicity. (Phase II)
OUTLINE:
- Nonmyeloablative-conditioning regimen: Patients receive busulfan IV on day -5 and
fludarabine IV over 30 minutes on days -4 to -2. Patients undergo total body irradiation
on day 0.
- Allogeneic peripheral blood stem cell transplantation (PBSC): Patients undergo donor
PBSC infusion on day 0.
- Graft-versus-host disease prophylaxis: Patients receive oral cyclosporine twice daily on
days -3 to 56 followed by a taper to day 180. Patients with a related stem cell donor
receive oral mycophenolate mofetil twice daily on days 0-28. Patients with an unrelated
stem cell donor receive oral mycophenolate mofetil 3 times daily on days 0-28 followed
by a taper twice daily to day 56. Patients with evidence of relapse or persistent
disease may also receive up to 3 donor lymphocyte infusions.
PROJECTED ACCRUAL: A total of 225 patients will be accrued for this study; 25 patients
accrued into the Phase I and 200 patients into Phase II.
Primary
- To assess safety and toxicity of the addition of busulfan added to an established
fludarabine and low-dose total-body irradiation (TBI) conditioning regimen for
non-myeloablative allogeneic transplantation in patients with hematologic malignancies.
(Phase I)
- To assess the non-relapse mortality 1-year after conditioning with busulfan and
fludarabine/TBI in patients with hematologic malignancies at moderate to high risk for
graft rejection and/or relapse of underlying disease. (Phase II)
Secondary
- To assess overall survival 1-year survival. (Phase II)
- To assess the incidence of graft rejection. (Phase II)
- To assess the incidence of grade II-IV acute graft-vs-host disease (GVHD) and chronic
extensive GVHD. (Phase II)
- To assess rates of disease progression and/or relapse-related mortality. (Phase II)
- To determine non-hematologic grade III-IV organ specific toxicity. (Phase II)
OUTLINE:
- Nonmyeloablative-conditioning regimen: Patients receive busulfan IV on day -5 and
fludarabine IV over 30 minutes on days -4 to -2. Patients undergo total body irradiation
on day 0.
- Allogeneic peripheral blood stem cell transplantation (PBSC): Patients undergo donor
PBSC infusion on day 0.
- Graft-versus-host disease prophylaxis: Patients receive oral cyclosporine twice daily on
days -3 to 56 followed by a taper to day 180. Patients with a related stem cell donor
receive oral mycophenolate mofetil twice daily on days 0-28. Patients with an unrelated
stem cell donor receive oral mycophenolate mofetil 3 times daily on days 0-28 followed
by a taper twice daily to day 56. Patients with evidence of relapse or persistent
disease may also receive up to 3 donor lymphocyte infusions.
PROJECTED ACCRUAL: A total of 225 patients will be accrued for this study; 25 patients
accrued into the Phase I and 200 patients into Phase II.
DISEASE CHARACTERISTICS:
- Diagnosis of a hematologic malignancy of 1 of the following high-risk types:
- Acute lymphoblastic leukemia
- Acute myeloid leukemia
- Chronic myelogenous leukemia
- Chronic lymphocytic leukemia
- Myelodysplastic syndromes
- Myeloproliferative disorder
- Multiple myeloma
- Plasma cell dyscrasias
- Non-Hodgkin lymphoma
- Hodgkin disease
PATIENT CHARACTERISTICS:
Performance status
- Karnofsky 50-100%
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- No liver failure
- No cirrhosis with evidence of portal hypertension
- No alcoholic hepatitis
- No esophageal varices
- No chronic hepatitis
- No other liver disease
Renal
- Not specified
Cardiovascular
- Left Ventricular Ejection Fraction (LVEF) > 35%
- No symptomatic coronary artery disease or cardiac failure requiring therapy
Pulmonary
- Diffusing capacity of lung for carbon monoxide (DLCO) > 30%
- Total lung capacity > 30%
- Forced expiratory volume in 1 second (FEV_1) > 30%
- No supplementary continuous oxygen
Other
- HIV negative
- No active nonhematologic malignancy except localized skin cancer
- No overt organ dysfunction
PRIOR CONCURRENT THERAPY:
- Not specified
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