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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00555048
• Other study ID #: 1981.00
• Secondary ID: P30CA015704FHCRC
• Status: Terminated
• Phase: Phase 1/Phase 2
• First received: November 6, 2007
• Last updated: January 4, 2011
• Start date: September 2007

Study information

• Verified date: January 2011
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 50 Years

Eligibility

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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

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

Intervention

Biological:
• alemtuzumab

Drug:
• busulfan

• cyclophosphamide

• methotrexate

• tacrolimus

Procedure:
• allogeneic hematopoietic stem cell transplantation

• peripheral blood stem cell transplantation

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Lowest dose of alemtuzumab associated with transplant-related mortality at day 180			No
Secondary	Life-threatening infection			No
Secondary	Grades III-IV acute graft-vs-host disease (GVHD)			No
Secondary	Survival at 1 year			No
Secondary	Disease relapse at 1 year			No
Secondary	Extensive chronic GVHD at 1 year			No
Secondary	Graft failure at day 100			No