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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


Phase 1/Phase 2
N/A
50 Years
Not Enrolling
Both
Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Diseases

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Trial Information

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


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.

Inclusion 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

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Outcome Measure:

Lowest dose of alemtuzumab associated with transplant-related mortality at day 180

Safety Issue:

No

Principal Investigator

Ann E. Woolfrey, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Food and Drug Administration

Study ID:

1981.00

NCT ID:

NCT00555048

Start Date:

September 2007

Completion Date:

Related Keywords:

  • Graft Versus Host Disease
  • Leukemia
  • Myelodysplastic Syndromes
  • Myelodysplastic/Myeloproliferative Diseases
  • 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
  • Graft vs Host Disease
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders
  • Myelodysplastic-Myeloproliferative Diseases

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Seattle Cancer Care AllianceSeattle, Washington  98109