NCT00914940

Selective Depletion of CD45RA+T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD

A Multi-center Phase II Study of Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts for the Prevention of GVHD

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 41 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 14 Years – 55 Years
• Healthy volunteers: Not accepted

Summary

RATIONALE: Allogeneic hematopoietic stem cell transplant (HSCT) is a treatment that can cure acute leukemia and myelodysplasia. After giving the patient chemotherapy and total body irradiation to stop the growth of cancer and remove the patient's diseased bone marrow, healthy stem cells from a donor are infused into the patient to replace the patient's bone marrow and make red and white blood cells and platelets. Unfortunately HSCT is often complicated by 'graft versus host disease' (GVHD) in which the transplanted cells from a donor can make an immune response against the body's normal cells and cause tissue damage and severe symptoms. Removing a subset of the donor T cells, called 'naive T cells', before transplant may reduce the frequency and intensity of GVHD. PURPOSE: This phase II trial will determine whether the removal of the naive T cells from donor cells can decrease the rate and severity of graft-vs-host disease while preserving specific immunity against infections in patients with acute leukemia or advanced myelodysplastic syndromes.

Detailed description

OBJECTIVES: Primary * Estimate the probability of grades II-IV acute graft-vs-host disease (GVHD) in patients with acute leukemia or advanced myelodysplastic syndromes treated with CD45RA+ T-cell-depleted allogeneic peripheral blood stem cell transplantation and compare this to relevant historical experience. * Estimate the probability of graft failure in these patients. Secondary * Evaluate immune reconstitution and pathogen-specific T-cell reconstitution in these patients. * Estimate the probability of transplant-related mortality by day 100 in these patients. * Estimate the probability of relapse in these patients. * Estimate the probability and severity of chronic GVHD in these patients. OUTLINE: This is a multicenter study. * Myeloablative conditioning regimen: Patients undergo total body irradiation twice daily for 4 days (Days -10 to -7) Patients also receive thiotepa IV over 4 hours for 2 days (Days -6 and -5) and fludarabine phosphate IV over 30 minutes for 5 days (Days -6 to -2.) * Transplantation: Patients receive a CD34+ enriched allogeneic peripheral blood stem cell (PBSC) product followed by a CD45RA+ T-cell-depleted allogeneic PBSC product on day 0. * Graft-vs-host disease (GVHD) prophylaxis: Patients will receive Tacrolimus as per cohort 1. If the rate of grade II-IV acute GVHD in the first 35 patients is significantly reduced (compared to historical controls), subsequent patients are enrolled in cohort 2. * Cohort 1: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 50, followed by a standard taper in the absence of grade II-IV acute GVHD. * Cohort 2: Patients receive tacrolimus IV continuously or orally twice daily beginning on day -1 and continuing until day 30, followed by a rapid taper in the absence of grade II-IV acute GVHD. Patients are followed actively for at least 1 year post transplant.

Conditions

• Graft Versus Host Disease
• Leukemia
• Myelodysplastic Syndromes

Interventions

Type	Name	Description
DRUG	Fludarabine Phosphate	Fludarabine will be administered in a dose of 25 mg/m2/day IV over approximately 30 minutes for 5 consecutive days (day -6 to -2). The total dose of fludarabine will be 125 mg/m2.
DRUG	Tacrolimus	Tacrolimus will be administered beginning on day -1 at a dose of 0.03 mg/kg/day by continuous IV infusion. For the first cohort of 35 patients, if there is no evidence of grade II-IV acute GVHD on or prior to day 50, tacrolimus should then be tapered at the rate of approximately 5% of the day 50 dose each week for liquid, and 20% of the day 50 dose per month for capsules. In the second cohort of 25 patients if there is no evidence of grade II GVHD on or prior to day 30, tacrolimus should then be tapered at the rate of approximately 8% of the day 30 dose each week for liquid, and 33% of the day 30 dose per month for capsules.
DRUG	Thiotepa	Thiotepa will be administered in a dose of 5 mg/kg/day (adjusted body weight) IV over approximately 4 hours for 2 consecutive days (day -6 and day -5).
RADIATION	Total-Body Irradiation (TBI)	TBI will be given as 165 cGy fractions twice per day x 4 days - total dose 1320cGy (days -10 to -7).
OTHER	Magnetic Affinity Cell Sorting	Device
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Patient will undergo a PBSC transplantation
PROCEDURE	Allogeneic Hematopoietic Stem Cell Transplantation	Patients who are considered appropriate candidates for allogeneic hematopoietic stem cell transplantation
BIOLOGICAL	T Cell-Depleted Hematopoietic Stem Cell Transplantation	Patients who are eligible will receive a T Cell-Depleted Hematopoietic Stem Cell Transplantation

Timeline

• Start date: 2009-12-17
• Primary completion: 2019-12-01
• Completion: 2020-05-26
• First posted: 2009-06-05
• Last updated: 2020-08-20
• Results posted: 2020-08-20

Locations

2 sites across 1 country: United States