Trials / Completed

CompletedNCT00104975

Alemtuzumab and Combination Chemotherapy Followed By Donor Lymphocytes in Treating Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

Reduced Intensity Conditioning Regimen for Haplo-identical Family Donor Stem Cell Transplants for Hematologic Malignancies With Delayed Add-back of Non-alloreactive T Cells

Status: Completed
Phase: Phase 1
Study type: Interventional
Enrollment: 20 (estimated)

Sponsor: Yale University · Academic / Other
Sex: All
Age: 18 Years – 55 Years
Healthy volunteers: Not accepted

Summary

RATIONALE: Giving low doses of chemotherapy before a donor peripheral blood stem cell transplant helps stop the growth of cancer cells. It also stops the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune system and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells that have been treated in the laboratory after the transplant may help increase this effect. Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus before and after transplant may stop this from happening. PURPOSE: This phase I trial is studying the side effects and best dose of donor lymphocytes when given after alemtuzumab and combination chemotherapy in treating patients who are undergoing donor stem cell transplant for hematologic cancer.

Detailed description

OBJECTIVES: * Determine the feasibility and efficacy of a reduced-intensity conditioning regimen comprising alemtuzumab, fludarabine, melphalan, and thiotepa followed by allogeneic peripheral blood stem cell transplantation (PBSCT) in patients with hematologic malignancies. * Determine the toxicity of this regimen in these patients. * Determine the safety of LMB-2 immunotoxin-treated, selectively-depleted donor T cells, administered after allogeneic PBSCT, in these patients. OUTLINE: This is a dose-escalation study of LMB-2 immunotoxin-treated, selectively-depleted donor T cells. * T cell preparation: Patients and donors undergo apheresis to obtain peripheral blood mononuclear cells (PBMCs), which are expanded in culture. Patients' PBMCs are irradiated and mixed with donor PBMCs. LMB-2 immunotoxin is added to the PBMCs in order to selectively deplete T cells from the donor PBMCs. * Conditioning: Patients receive alemtuzumab IV over 2 hours on days -9 to -5, fludarabine IV over 30 minutes on days -8 to -5, melphalan IV over 15-20 minutes on day -4, and thiotepa IV on days -3 to -2. * Immunosuppression: Patients receive tacrolimus IV continuously on days -10 to 1. * Allogeneic peripheral blood stem cell (PBSC) transplantation: Patients undergo allogeneic PBSC transplantation on day 0. * LMB-2 immunotoxin-treated, selectively-depleted donor T cells: Patients receive LMB-2 immunotoxin-treated, selectively-depleted donor T cells IV over 30-60 minutes on approximately day 28. Cohorts of 3-6 patients receive escalating dose of LMB-2 immunotoxin-treated, selectively-depleted donor T cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting-toxicity. After completion of study treatment, patients are followed weekly for 100 days post-transplantation and then periodically for survival. PROJECTED ACCRUAL: A total of 15-20 patients will be accrued for this study.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	alemtuzumab
BIOLOGICAL	therapeutic allogeneic lymphocytes
DRUG	fludarabine phosphate
DRUG	melphalan
DRUG	tacrolimus
DRUG	thiotepa
PROCEDURE	peripheral blood stem cell transplantation

Timeline

Start date: 2005-02-01
Primary completion: 2008-05-01
Completion: 2008-05-01
First posted: 2005-03-04
Last updated: 2016-12-15

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT00104975. Inclusion in this directory is not an endorsement.