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

This study has been terminated.
(Low accrual)
Sponsor:
Collaborator:
Information provided by:
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT00555048
First received: November 6, 2007
Last updated: January 4, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention Phase
Graft Versus Host Disease
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Biological: alemtuzumab
Drug: busulfan
Drug: cyclophosphamide
Drug: methotrexate
Drug: tacrolimus
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: peripheral blood stem cell transplantation
Phase 1
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Prospective Trial to Evaluate the Role of In Vivo T Cell Depletion by Campath® (Alemtuzumab) in Reduction of Transplant Related Mortality in Transplantation From HLA-Class I or Class II Mismatched, Unrelated Donors

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Lowest dose of alemtuzumab associated with transplant-related mortality at day 180 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Life-threatening infection [ Designated as safety issue: No ]
  • Grades III-IV acute graft-vs-host disease (GVHD) [ Designated as safety issue: No ]
  • Survival at 1 year [ Designated as safety issue: No ]
  • Disease relapse at 1 year [ Designated as safety issue: No ]
  • Extensive chronic GVHD at 1 year [ Designated as safety issue: No ]
  • Graft failure at day 100 [ Designated as safety issue: No ]

Enrollment: 1
Study Start Date: September 2007
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Detailed 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.

  Eligibility

Ages Eligible for Study:   up to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00555048

Locations
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States, 98104-1024
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109-1023
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Ann E. Woolfrey, MD Fred Hutchinson Cancer Research Center
  More Information

No publications provided

Responsible Party: Ann E. Woolfrey, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00555048     History of Changes
Other Study ID Numbers: 1981.00, P30CA015704, FHCRC-1981.00, CDR0000574145
Study First Received: November 6, 2007
Last Updated: January 4, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Fred Hutchinson Cancer Research Center:
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

Additional relevant MeSH terms:
Graft vs Host Disease
Leukemia
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Immune System Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Alemtuzumab
Busulfan
Cyclophosphamide
Methotrexate
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists

ClinicalTrials.gov processed this record on October 30, 2014