Cyclophosphamide Plus Transplantation of Partially HLA-Mismatched (Haploidentical), CD8+ T Cell-Depleted Peripheral Blood Cells (PBCs) for Patients With Myelodysplastic (MDS) or Myeloproliferative Disorders (MPD)
18 Years
N/A
Both
Leukemia, Myelodysplastic Syndromes
Trial Information
Cyclophosphamide Plus Transplantation of Partially HLA-Mismatched (Haploidentical), CD8+ T Cell-Depleted Peripheral Blood Cells (PBCs) for Patients With Myelodysplastic (MDS) or Myeloproliferative Disorders (MPD)
OBJECTIVES:
- Determine the maximum tolerated dose of allogeneic CD8-positive T-cell-depleted,
haploidentical donor lymphocytes when given after cyclophosphamide in patients with
myelodysplastic syndromes or myeloproliferative disorders.
OUTLINE: Patients receive cyclophosphamide on days 1 and 2. Patients then undergo infusion
of allogeneic T-cell depleted donor lymphocytes on day 3.
Cohorts of patients receive escalating doses of CD8-positive T-cell-depleted haploidentical
donor lymphocytes until the maximum tolerated dose is determined.
PROJECTED ACCRUAL: A total of 44 patients will be accrued for this study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following:
- Myelodysplastic syndromes (MDS)
- International Prognostic Scoring System (IPSS) score ≥ intermediate-2
- Chronic myelomonocytic leukemia
- Acute myeloid leukemia arising from MDS
- Must have failed or are ineligible for or intolerant to treatment with azacitidine
- Patients with normal marrow cytogenetics or an isolated 5q- abnormality must
have failed or are ineligible for or intolerant to treatment with lenalidomide
- Patients who are HLA-DR15-positive must have failed or are ineligible for
pharmacologic immunosuppression (e.g., anti-thymocyte globulin, cyclosporine,
steroids)
- No presence of cytotoxic antibodies against donor lymphocytes
- No HLA-identical donor available OR ineligible for HLA-identical allogeneic bone
marrow transplantation
- HLA partially mismatched (haploidentical) related donor available
- First-degree related donor, including half-siblings or first cousins
- Inherited recombinant haplotype from parents allowed if donor shares ≥ 1 HLA
antigen at each of the HLA-A, -B, and DR loci
PATIENT CHARACTERISTICS:
- ECOG performance status (PS) 0-1 OR Karnofsky PS 80-100%
- Bilirubin < 3.0 mg/dL
- AST and ALT ≤ 4 times upper limit of normal
- Creatinine < 3.0 mg/dL
- LVEF > 35%
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- Recovered from prior therapy
- No prior transfusions from donor
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin C)
or radiotherapy
- No other concurrent investigational drugs
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of CD8-positive T-cell-depleted haploidentical donor lymphocytes
Safety Issue:
Yes
Principal Investigator
Yvette L. Kasamon, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Sidney Kimmel Comprehensive Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
J0551 CDR0000483771
NCT ID:
NCT00356928
Start Date:
May 2006
Completion Date:
May 2011
Related Keywords:
- Leukemia
- Myelodysplastic Syndromes
- previously treated myelodysplastic syndromes
- secondary myelodysplastic syndromes
- secondary acute myeloid leukemia
- chronic myelomonocytic leukemia
- de novo myelodysplastic syndromes
- Leukemia
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Myelodysplastic Syndromes
- Preleukemia
- Myeloproliferative Disorders
Name | Location |
|---|---|
| Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Baltimore, Maryland 21231-2410 |
