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
18 Years
80 Years
Both
Chronic Myeloproliferative Disorders, Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms, Precancerous Condition
Trial Information
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
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 200 patients will be accrued for this study.
Inclusion Criteria
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
- LVEF > 35%
- No symptomatic coronary artery disease or cardiac failure requiring therapy
Pulmonary
- DLCO > 30%
- Total lung capacity > 30%
- 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
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Safety
Outcome Description:
Evaluations at 6 months, 12 months, 18 months and subsequent yearly follow-up's for a total of 5 years.
Outcome Time Frame:
5 years
Safety Issue:
Yes
Principal Investigator
Richard Maziarz, MD
Investigator Role:
Study Chair
Investigator Affiliation:
OHSU Knight Cancer Institute
Authority:
United States: Institutional Review Board
Study ID:
CDR0000447204
NCT ID:
NCT00245037
Start Date:
June 2005
Completion Date:
Related Keywords:
- Chronic Myeloproliferative Disorders
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- Myelodysplastic/Myeloproliferative Neoplasms
- Precancerous Condition
- recurrent adult acute lymphoblastic leukemia
- recurrent adult acute myeloid leukemia
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- atypical chronic myeloid leukemia, BCR-ABL negative
- refractory chronic lymphocytic leukemia
- stage III chronic lymphocytic leukemia
- stage IV chronic lymphocytic leukemia
- accelerated phase chronic myelogenous leukemia
- blastic phase chronic myelogenous leukemia
- chronic phase chronic myelogenous leukemia
- relapsing chronic myelogenous leukemia
- stage II multiple myeloma
- stage III multiple myeloma
- primary systemic amyloidosis
- refractory multiple myeloma
- myelodysplastic/myeloproliferative neoplasm, unclassifiable
- chronic eosinophilic leukemia
- primary myelofibrosis
- chronic neutrophilic leukemia
- essential thrombocythemia
- polycythemia vera
- chronic myelomonocytic leukemia
- acute undifferentiated leukemia
- extramedullary plasmacytoma
- isolated plasmacytoma of bone
- monoclonal gammopathy of undetermined significance
- stage I multiple myeloma
- secondary acute myeloid leukemia
- 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)
- 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
- 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 small lymphocytic lymphoma
- 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
- extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- Neoplasms
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
- Precancerous Conditions
- Lymphoma, Large-Cell, Immunoblastic
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| Knight Cancer Institute at Oregon Health and Science University | Portland, Oregon 97239-3098 |
