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

Phase 1

Terminated

• Conditions: Graft Versus Host Disease; Leukemia; Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Diseases
• Interventions: Biological: alemtuzumab; Drug: busulfan; Drug: cyclophosphamide; Drug: methotrexate; Drug: tacrolimus; Procedure: allogeneic hematopoietic stem cell transplantation; Procedure: peripheral blood stem cell transplantation

• Registration Number: NCT00555048
• Lead Sponsor: Fred Hutchinson Cancer Center

Brief 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.

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.

Study Timeline

• Study Start: 2007-09
• Study First Submitted: 2007-11-06
• Study First Submitted QC: 2007-11-06
• Study First Posted: 2007-11-07
• Primary Completion: 2010-10
• Status Verified: 2017-04
• Results First Submitted: 2017-04-17
• Results First Submitted QC: 2017-04-17
• Last Update Submitted: 2017-04-17
• Results First Posted: 2017-05-24
• Last Update Posted: 2017-05-24

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Alemtuzumab	alemtuzumab	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant.
Alemtuzumab	busulfan	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant.
Alemtuzumab	cyclophosphamide	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant.
Alemtuzumab	methotrexate	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant.
Alemtuzumab	tacrolimus	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant.
Alemtuzumab	allogeneic hematopoietic stem cell transplantation	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant.
Alemtuzumab	peripheral blood stem cell transplantation	Alemtuzumab given together with busulfan and cyclophosphamide followed by a donor stem cell transplant.

Primary Outcome Measures

Name	Time	Method
Lowest Dose of Alemtuzumab Associated With Transplant-related Mortality	Up to day 180	Lowest dose of alemtuzumab associated with transplant-related mortality at day 180

Secondary Outcome Measures

Name	Time	Method
Extensive Chronic GVHD	Up to 1 year	Count of participants with extensive chronic GVHD at 1 year
Graft Failure	Up to day 100	Count of participants with graft failure at day 100
Disease Relapse	Up to 1 year	Count of participants with disease relapse at 1 year
Life-threatening Infection	Up to 180 days
Grades III-IV Acute Graft-vs-host Disease (GVHD)	Up to 100 days
Overall Survival	Up to 1 year	Count of surviving participants at 1 year

Trial Locations

Locations (2)

Fred Hutchinson Cancer Research Center; 🇺🇸 Seattle, Washington, United States

Seattle Cancer Care Alliance; 🇺🇸 Seattle, Washington, United States