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

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.

Conditions

• Graft Versus Host Disease
• Leukemia
• Myelodysplastic Syndromes

Interventions

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

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• Fred Hutchinson Cancer Center

  lead OTHER

Principal Investigators

• Marie Bleakley, MD · Fred Hutchinson Cancer Center

• Warren Shlomchik, MD · Yale University School of Medicine/Yale New Haven Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

14 Years

Max Age

55 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2009-12-17

Primary Completion

2019-12-01

Completion

2020-05-26

Countries

• United States

Study Locations