HLA-HAPLOIDENTICAL FAMILIAL DONOR HEMATOPOIETIC CELL TRANSPLANTATION AFTER REDUCED INTENSITY CONDITIONING OF BUSULFAN, FLUDARABINE, AND ANTI-THYMOCYTE GLOBULIN FOR ADULT PATIENTS WITH HEMATOLOGIC MALIGNANCIES AND MYELODYSPLASTIC SYNDROME - A PHASE 2 STUDY
N/A
75 Years
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
HLA-HAPLOIDENTICAL FAMILIAL DONOR HEMATOPOIETIC CELL TRANSPLANTATION AFTER REDUCED INTENSITY CONDITIONING OF BUSULFAN, FLUDARABINE, AND ANTI-THYMOCYTE GLOBULIN FOR ADULT PATIENTS WITH HEMATOLOGIC MALIGNANCIES AND MYELODYSPLASTIC SYNDROME - A PHASE 2 STUDY
OBJECTIVES:
- To evaluate the efficacy of HLA-haploidentical familial donor hematopoietic cell
transplantation with a reduced-intensity conditioning regimen of busulfan, fludarabine
phosphate, and anti-thymocyte globulin in patients with hematologic malignancies or
myelodysplastic syndromes.
OUTLINE: Before receiving the reduced-intensity conditioning regimen, patients receive one
dose of intrathecal (IT) methotrexate, then leucovorin calcium IV or orally 4 hours after
methotrexate and every 6 hours for a total of 8 doses.
- Reduced-intensity conditioning regimen: Patients receive busulfan IV over 6 hours on
days -7 and -6, fludarabine phosphate IV over 30 minutes on days -7 to -2,
anti-thymocyte globulin (ATG) IV over 4 hours on days -4 to -1, and methylprednisolone
IV over 30 minutes on days -4 to -1.
- HLA-haploidentical familial donor hematopoietic stem cell transplantation (HSCT):
Patients undergo allogeneic HSCT over 1 hour on days 0 and 1.
- Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV* over
2-4 hours every 12 hours on days -1 to 30 followed by a taper until day 60 and
methotrexate IV on days 2, 4 , 7, and 12.
NOTE: *Cyclosporine can be given orally once oral medication can be tolerated
- CNS prophylaxis: When blood counts recover, patients with acute leukemia or chronic
myelogenous leukemia in blastic crisis resume IT methotrexate once every 2 weeks for a
total of 4 doses (including the dose given before the conditioning regimen) and
leucovorin calcium IV or orally 4 hours after (each dose of methotrexate) and every 6
hours for a total of 8 doses.
After completion of study treatment, patients are followed periodically for up to 3 years.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following hematological malignancies:
- Acute leukemia, including any of the following:
- Refractory acute leukemia
- Acute leukemia beyond first remission
- Acute leukemia in first remission with intermediate to poor prognostic
features as suggested by chromosomal findings
- Chronic myelogenous leukemia (CML)
- Second chronic phase
- Accelerated phase
- Blastic phase
- Myelodysplastic syndrome (MDS)
- High-risk MDS (refractory anemia with excess blasts [RAEB], RAEB in
transformation, and chronic myelomonocytic leukemia) can be transplanted
without prior therapy or after prior therapy failure with hypomethylating
agents
- Low-risk MDS can be considered for transplantation after prior therapy
failure with immunosuppressive or hypomethylating agents
- No willing, suitable HLA-matched donor in family or in donor registries
- Patients with active hematologic malignancy, who are felt to be in urgent need
of allogeneic hematopoietic cell transplantation, can enroll without a search
for HLA-matched unrelated donors
- Related donor with HLA-haploidentical mismatch at 3 or less of 6 loci available
PATIENT CHARACTERISTICS:
- Karnofsky performance status 70-100%
- Bilirubin < 2.0 mg/dL
- Creatinine < 2.0 mg/dL
- AST < 3 times upper limit of normal
- Ejection fraction > 40% by MUGA
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
tumor response
Outcome Description:
leukemia CR, CR duration
Outcome Time Frame:
about 4-8 weeks after transplantation
Safety Issue:
No
Principal Investigator
Kyoo H. Lee, MD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Asan Medical Center
Authority:
Korea: Food and Drug Administration
Study ID:
CDR0000600347
NCT ID:
NCT00732316
Start Date:
April 2008
Completion Date:
May 2011
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- accelerated phase chronic myelogenous leukemia
- adult acute lymphoblastic leukemia in remission
- adult acute myeloid leukemia in remission
- acute undifferentiated leukemia
- blastic phase chronic myelogenous leukemia
- childhood acute lymphoblastic leukemia in remission
- childhood acute myeloid leukemia in remission
- childhood chronic myelogenous leukemia
- childhood myelodysplastic syndromes
- chronic phase chronic myelogenous leukemia
- chronic myelomonocytic leukemia
- de novo myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- recurrent childhood acute lymphoblastic leukemia
- recurrent childhood acute myeloid leukemia
- recurrent adult acute lymphoblastic leukemia
- recurrent adult acute myeloid leukemia
- refractory anemia with excess blasts
- refractory anemia with excess blasts in transformation
- relapsing chronic myelogenous leukemia
- secondary myelodysplastic syndromes
- Leukemia
- Myelodysplastic Syndromes
- Preleukemia
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