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

Fred Hutchinson Cancer Center (FHCC)

Status and phase

Terminated

Phase 2

Phase 1

Conditions

Graft Versus Host Disease

Leukemia

Myelodysplastic/Myeloproliferative Diseases

Myelodysplastic Syndromes

Treatments

Drug: busulfan

Procedure: peripheral blood stem cell transplantation

Drug: tacrolimus

Procedure: allogeneic hematopoietic stem cell transplantation

Drug: cyclophosphamide

Drug: methotrexate

Biological: alemtuzumab

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00555048

FHCRC-1981.00

CDR0000574145 (Registry Identifier)

P30CA015704 (U.S. NIH Grant/Contract)

1981.00

Details and patient eligibility

About

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.

Full description

OBJECTIVES:

Primary

Identify the lowest dose of alemtuzumab that is associated with day 180 transplant-related mortality ≤ 45%.

Secondary

Determine the incidence of life-threatening infection in patients receiving this treatment.
Determine the incidence of grades III-IV acute graft-vs-host disease (GVHD) in patients receiving this treatment.
Determine the survival at 1 year in patients receiving this treatment.
Determine the incidence of disease relapse at 1 year in patients receiving this treatment.
Determine the incidence of extensive chronic GVHD at 1 year in patients receiving this treatment.
Determine the incidence of graft failure at day 100 in patients receiving this treatment.

OUTLINE:

Chemotherapy: Patients receive alemtuzumab IV over 2 hours on days -10 to -6, busulfan IV over 3 hours on days -7 to -4, and cyclophosphamide IV on days -3 and -2.
Peripheral blood stem cell (PBSC) transplantation: Patients undergo allogeneic filgrastim (G-CSF)-mobilized PBSC transplantation on day 0.
Graft-vs-host disease prophylaxis: Patients receive tacrolimus IV continuously or orally twice daily on days -1 to 50 and methotrexate IV on days 1, 3, 6, and 11.

After completion of study therapy, patients are followed periodically.

Enrollment

1 patient

Sex

All

Ages

Under 50 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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