Alemtuzumab, Busulfan, and Cyclophosphamide Followed By a Donor Stem Cell Transplant in Treating Patients With Hematologic Cancer

• Status: Terminated
• Trial end date: 1969-12-31
• Target enrollment: 0
• Participant gender: All

Summary

RATIONALE: Monoclonal antibodies, such as alemtuzumab, can find cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving chemotherapy drugs, such as busulfan and cyclophosphamide, before a donor stem cell transplant helps stop the growth of cancer cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving tacrolimus and methotrexate after the transplant may stop this from happening.

PURPOSE: This phase I/II trial is studying the best dose of alemtuzumab when given together with busulfan and cyclophosphamide followed by a donor stem cell transplant and to see how well it works in treating patients with hematologic cancer.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Fred Hutchinson Cancer Research Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Alemtuzumab; Busulfan; Cyclophosphamide; Methotrexate; Tacrolimus

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