Alemtuzumab, Busulfan, and Cyclophosphamide Followed By a Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer
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 megakaryoblastic leukemia (M7), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myelomonocytic leukemia (M4), adult acute promyelocytic leukemia (M3), adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), childhood acute megakaryocytic leukemia (M7), childhood acute monoblastic leukemia (M5a), childhood acute monocytic leukemia (M5b), childhood acute myeloblastic leukemia with maturation (M2), childhood acute myeloblastic leukemia without maturation (M1), childhood acute myelomonocytic leukemia (M4), childhood acute promyelocytic leukemia (M3), accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, 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), blastic phase chronic myelogenous leukemia, childhood acute lymphoblastic leukemia in remission, childhood acute myeloid leukemia in remission, childhood chronic myelogenous leukemia, chronic phase chronic myelogenous leukemia, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent childhood acute lymphoblastic leukemia, recurrent childhood acute myeloid leukemia, relapsing chronic myelogenous leukemia, secondary acute myeloid leukemia, childhood myelodysplastic syndromes, de novo myelodysplastic syndromes, myelodysplastic/myeloproliferative diseases, secondary myelodysplastic syndromes
Eligibility Criteria
DISEASE CHARACTERISTICS:
Confirmed diagnosis of one of the following:
Primary acute myeloid leukemia (AML) meeting any of the following criteria:
First complete remission (CR; defined as < 5% blasts in marrow) with high-risk features as defined by failure to achieve remission by day 21 after induction chemotherapy, or the presence of chromosomal abnormalities involving any of the following:
- -5/del(5q)
- -7/del(7q)
- Inversion 3q
- Abnormalities of 11q23, 20q, 21q, del(9q),
- Translocation 6;9
- Translocation 9;22
- Abnormalities of 17p
- Complex karyotype with ≥ 3 abnormalities
- Second CR or subsequent in remission
- Refractory or relapsed disease
- Secondary AML in remission or relapse
Chronic myelogenous leukemia (CML) in accelerated or blast phase meeting the following criteria:
Accelerated phase is defined by any one of the following:
- Blasts 10% to 19% of peripheral blood white cells or bone marrow cells
- Peripheral blood basophils ≥ 20%
- Persistent thrombocytopenia (< 100,000/mm³) unrelated to therapy, or persistent thrombocytosis (> 1,000,000/mm³) unresponsive to therapy
- Increasing spleen size and increasing WBC count unresponsive to therapy
- Cytogenetic evidence of clonal evolution (i.e., the appearance of an additional genetic abnormality that was not present in the initial specimen at the time of diagnosis of chronic phase CML)
Blast phase is defined by any of the following:
- Blasts ≥ 20% of peripheral blood white cells or bone marrow cells
- Extramedullary blast proliferation
- Large foci or clusters of blasts in bone marrow biopsy
- Primary myelodysplastic syndromes (MDS) with an IPSS score > 1.5
- Secondary MDS with any IPSS score
Primary acute lymphoblastic leukemia meeting any of the following criteria:
First CR (< 5% blasts in marrow) with high-risk features as defined by 1 of the following:
- Failure to achieve remission after first induction chemotherapy
- Presence of chromosomal abnormalities including hypodiploidy or abnormalities of 11q23 or translocation 9;22
- Second CR or subsequent in remission
- Refractory or relapsed disease
- No patients for whom a suitable HLA genotypically identical sibling or fully matched HLA-A, -B, -C, and -DRB1 unrelated donor is available
- No active CNS involvement with disease
Donors must meet the following criteria:
Unrelated volunteer donors who are mismatched for more than one HLA-class I alleles or antigens or for one HLA-class I antigen, but matched by high-resolution typing at HLA-DRB1 and -DQB1, OR who are mismatched for one or more HLA-class II alleles or antigens, but matched by high-resolution typing at HLA-A, -B, and -C
- No two-antigen mismatch at a single HLA-A, -B, or -C locus
- No mismatching of class I and class II HLA
- Matching must be based on results of high-resolution typing at HLA-A, -B, -C, - DRB1, and -DQB1
PATIENT CHARACTERISTICS:
- Karnofsky performance status 50-100%
- No symptomatic coronary artery disease or symptomatic congestive heart failure
- No hepatic disease with transaminases or bilirubin > 2 times upper limit of normal except for isolated hyperbilirubinemia attributed to Gilbert's syndrome
- No severe hypoxemia with room air P_AO_2 < 70, supplemental oxygen-dependence, or DLCO < 60% predicted
- No impaired renal function with creatinine > 2 times upper limit of normal or creatinine clearance < 50% normal
- Not HIV seropositive
- Not pregnant or breast-feeding
- Fertile patients must use effective contraception
- No active infections that are untreated or failing to respond to appropriate therapy
PRIOR CONCURRENT THERAPY:
Inclusion criteria:
- See Disease Characteristics
Exclusion criteria:
- Prior allogeneic or autologous bone marrow, peripheral blood stem cell, or umbilical cord blood transplantation using a high-dose total-body irradiation regimen
Sites / Locations
- Fred Hutchinson Cancer Research Center
- Seattle Cancer Care Alliance
Arms of the Study
Arm 1
Experimental
Alemtuzumab
Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant.