Clofarabine, Melphalan, and Thiotepa Followed By a Donor Stem Cell Transplant in Treating Patients With High-Risk and/or Advanced Hematologic Cancer or Other Disease
Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes
About this trial
This is an interventional treatment trial for Graft Versus Host Disease focused on measuring graft versus host disease, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, childhood acute lymphoblastic leukemia in remission, childhood chronic myelogenous leukemia, recurrent childhood acute myeloid leukemia, accelerated phase chronic myelogenous leukemia, acute undifferentiated leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, blastic phase chronic myelogenous leukemia, juvenile myelomonocytic leukemia, previously treated myelodysplastic syndromes, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, secondary myelodysplastic syndromes, childhood acute myeloid leukemia in remission, de novo myelodysplastic syndromes, recurrent childhood acute lymphoblastic leukemia, chronic phase chronic myelogenous leukemia, 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), childhood myelodysplastic syndromes
Eligibility Criteria
DISEASE CHARACTERISTICS:
Histologically or cytologically confirmed diagnosis of 1 of the following:
Acute myelogenous leukemia, meeting 1 of the following criteria:
In first complete remission (CR), meeting 1 of the following criteria:
- Poor risk [no t(15,17), inv 16, or t(8,21)]
- Not a candidate for total body irradiation (TBI)
- Any infant in first CR
In second CR, meeting the following criteria:
- All patients
In more than second CR OR relapsed/refractory disease, meeting the following criteria:
- All patients
- Blast percentage > 5% and < 25% in bone marrow (BM) at the time of stem cell transplantation (SCT)
Acute lymphoblastic leukemia, meeting 1 of the following criteria:
In first CR, meeting 1 of the following criteria:
- Poor risk [t(9;22), t(4;11) AND no CR after 7-28 days of induction]
- Not a candidate for TBI
- Any infant in first CR
In second CR, meeting the following criteria:
- All patients
In more than second CR OR relapsed/refractory disease, meeting the following criteria:
- All patients
- Blast percentage > 5% and < 25% in BM at the time of SCT
Acute undifferentiated or biphenotypic leukemia, meeting the following criteria:
- All patients
- Blast percentage > 5% and < 25% in BM at the time of SCT
Chronic myelogenous leukemia, meeting the following criteria:
- All patients
- In first chronic phase
Myelodysplastic syndrome, meeting 1 of the following criteria:
Primary high risk disease
- Stage > RAEB1
Secondary high risk disease
- All patients
- Any stage
Juvenile myelomonocytic leukemia
- All patients
- No doubling of peripheral blast counts within a period of 2 weeks
- No active CNS disease
HLA-compatible donor available meeting 1 of the following criteria:
Related donor
- Genotypically or phenotypically matched at ≥ 7 or 8 of HLA-A, -B, -C and -DRB1 alleles
Unrelated donor meeting 1 of the following criteria:
- 8 of 8 alleles matched
- For patients < 18 years old only: 7 or 8 alleles matched with the mismatch at only 1 HLA-A, -B, -C, or -DRB1 allele
Two HLA-compatible unrelated cord blood (UCB) units available meeting the following criteria:
HLA-matched minimally at 4 of 6 HLA-A, HLA-B, and DRB1 allele
- HLA-A and HLA-B matched at intermediate resolution by molecular technique
- DRB1 allele matched at high resolution by molecular technique
- Both matched UCB units with cryopreserved nucleated cell dose ≥ 1.5 x 10^7/kg
PATIENT CHARACTERISTICS:
- Karnofsky OR Lansky performance status 70-100%
- SGOT < 2 times upper limit of normal
- Bilirubin < 1.5 mg/dL (unless there is liver disease involvement)
- Creatinine normal OR creatinine clearance > 60 mL/min
- LVEF > 50% at rest OR shortening fraction ≥ 29%
- Patients with asymptomatic pulmonary disease with no prior risk factors OR symptomatic pulmonary disease with diffusion capacity > 50% of predicted (corrected for hemoglobin) are eligible
- No active uncontrolled viral, bacterial, or fungal infection
- No known HIV I or II positivity
- No known human T-cell lymphotrophic virus I or II positivity
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
PRIOR CONCURRENT THERAPY:
- No hydroxyurea within the past 2 weeks
- No allogeneic or autologous stem cell transplantation within the past 6 months
Sites / Locations
- Memorial Sloan-Kettering Cancer Center
Arms of the Study
Arm 1
Experimental
cytoreduction regimen & stem cell transplant
This is a single arm phase I/II clinical trial to assess efficacy (the antileukemic potential and relapse rate), and safety (peri-transplant morbidity and mortality) of a novel cytoreduction regimen in preparation for allogeneic hematopoietic stem cell transplantation (HSCT).