Pilot Study Of T-Cell-Depleted Peripheral Blood Stem Cell Transplantation From Partially Matched Related Donors For Patients With High-Risk Leukemia
10 Years
50 Years
Both
Chronic Myeloproliferative Disorders, Leukemia, Myelodysplastic/Myeloproliferative Diseases
Trial Information
Pilot Study Of T-Cell-Depleted Peripheral Blood Stem Cell Transplantation From Partially Matched Related Donors For Patients With High-Risk Leukemia
OBJECTIVES:
- Determine the safety of a preparative regimen comprising total body irradiation,
cyclophosphamide, thiotepa, and fludarabine, but without anti-thymocyte globulin, in
patients with high-risk leukemia treated with peripheral blood stem cell
transplantation from partially matched related donors.
- Determine the incidence of graft failure, acute graft-versus-host disease (GVHD), and
treatment-related mortality in patients treated with this regimen.
- Determine rates of chronic GVHD and relapse in patients treated with this regimen.
- Determine disease-free and overall survival in patients treated with this regimen.
OUTLINE: This is a pilot study.
Patients receive a preparative regimen comprising total lymphoid irradiation once daily on
days -13 to -11; cyclophosphamide IV over 1 hour on days -8 and -7; thiotepa IV over 4 hours
every 12 hours on day -6; fludarabine IV over 30 minutes on days -5 to -1; and total body
irradiation once on day -1. Patients also receive cyclosporine IV over 12 hours on days -8
to -1 and methylprednisolone IV twice daily on days -3 and -2. Patients receive
CD34-enriched T-cell-depleted allogeneic stem cell infusion on day 0.
Patients with disease progression or uncontrolled infection but without grade II or greater
graft-versus-host disease may receive up to 3 donor lymphocyte infusions at least 4 weeks
apart until disease regression.
Patients are followed at least weekly until day 100 and then at 6, 12, 18, 24, 36, and 48
months.
PROJECTED ACCRUAL: A total of 20-51 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following:
- High-risk myelodysplastic syndromes (MDS), meeting 1 of the following criteria:
- Transformation to acute leukemia defined by at least 15% blasts
- Secondary to prior treatment with chemotherapy and/or radiotherapy
- Presence of complex cytogenetics (at least 3 karyotypic abnormalities)
- Monosomy or deletion of chromosome 7
- Acute myeloid leukemia (AML), meeting 1 of the following criteria :
- High-risk AML in first remission and meeting 1 of the following criteria:
- At least 3 karyotypic abnormalities
- Monosomy or deletion of chromosome 5 or 7 = 11q23 chromosomal
abnormality
- Prior diagnosis of MDS
- Received prior radiotherapy or chemotherapy
- In second or subsequent remission
- Primary induction failure or partial remission
- Untested or sensitive relapse
- Chronic myelogenous leukemia, meeting 1 of the following criteria:
- Blast crisis
- Accelerated phase disease that has failed prior treatment with imatinib
mesylate, defined as a failure to achieve hematologic response after 3
months of standard dose (600 mg/day) therapy or disease progression on
therapy
- Myeloproliferative disease
- The following diagnoses are eligible:
- Agnogenic myeloid metaplasia
- Essential thrombocythemia
- Polycythemia vera
- Must have evidence of transformation to acute leukemia
- Acute lymphocytic leukemia (ALL), meeting 1 of the following criteria:
- High-risk ALL in first remission defined by 1 of the following:
- t(9;22) or 11q23 chromosomal abnormality
- Complete response at least 4 weeks after induction therapy OR
requiring at least 2 induction regimens
- Second or subsequent remission
- No relapsed leukemia refractory to appropriate salvage therapy
- Availability of an HLA-mismatched family donor
- Donor age 75 or under
- No better donor alternative (i.e., HLA-matched related or unrelated stem cell donor)
is available
PATIENT CHARACTERISTICS:
Age
- 10 to 50
Performance status
- ECOG 0-1
Life expectancy
- More than 3 months
Hematopoietic
- See Disease Characteristics
Hepatic
- Bilirubin no greater than 4 mg/dL
- Transaminases no greater than 3 times upper limit of normal
Renal
- Creatinine no greater than 2.0 mg/dL OR
- Creatinine clearance at least 60 mL/min
Cardiovascular
- LVEF at least 40%
Pulmonary
- DLCO at least 65% of predicted
Other
- Not pregnant
- Negative pregnancy test
- HIV negative
- No other prior malignancy except basal cell or squamous cell skin cancer or a remote
history of cancer now considered cured
- No major organ dysfunction that would preclude transplantation
- No major anticipated illness or organ failure that would preclude transplantation
- No severe psychiatric illness or mental deficiency that would preclude giving
informed consent or complying with study
- No uncontrolled infection
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- See Disease Characteristics
Endocrine therapy
- Not specified
Radiotherapy
- See Disease Characteristics
Surgery
- Not specified
Type of Study:
Interventional
Study Design:
Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Incidence of graft failure 100 days post-transplant
Principal Investigator
Bipin N. Savani, MD
Investigator Role:
Study Chair
Investigator Affiliation:
National Heart, Lung, and Blood Institute (NHLBI)
Authority:
Unspecified
Study ID:
CDR0000315900
NCT ID:
NCT00066417
Start Date:
Completion Date:
January 2007
Related Keywords:
- Chronic Myeloproliferative Disorders
- Leukemia
- Myelodysplastic/Myeloproliferative Diseases
- essential thrombocythemia
- polycythemia vera
- blastic phase chronic myelogenous leukemia
- secondary myelodysplastic syndromes
- previously treated myelodysplastic syndromes
- adult acute myeloid leukemia in remission
- childhood acute myeloid leukemia in remission
- de novo myelodysplastic syndromes
- secondary acute myeloid leukemia
- accelerated phase chronic myelogenous leukemia
- childhood chronic myelogenous leukemia
- adult acute lymphoblastic leukemia in remission
- childhood acute lymphoblastic leukemia in remission
- recurrent adult acute myeloid leukemia
- relapsing chronic myelogenous leukemia
- recurrent childhood acute myeloid leukemia
- chronic idiopathic myelofibrosis
- atypical chronic myeloid leukemia
- myelodysplastic/myeloproliferative disease, unclassifiable
- adult acute myeloid leukemia with t(8;21)(q22;q22)
- adult acute myeloid leukemia with t(16;16)(p13;q22)
- adult acute myeloid leukemia with inv(16)(p13;q22)
- adult acute myeloid leukemia with 11q23 (MLL) abnormalities
- adult acute myeloid leukemia with t(15;17)(q22;q12)
- Leukemia
- Myeloproliferative Disorders
- Myelodysplastic-Myeloproliferative Diseases
Name | Location |
|---|---|
| NIH - Warren Grant Magnuson Clinical Center | Bethesda, Maryland 20892-1182 |
