Selective Depletion of CD45RA+ T Cells From Allogeneic Peripheral Blood Stem Cell Grafts From HLA-Matched Related and Unrelated Donors in Preventing GVHD

Summary

This phase II trial is for patients with acute lymphocytic leukemia, acute myeloid leukemia, myelodysplastic syndrome or chronic myeloid leukemia who have been referred for a peripheral blood stem cell transplantation to treat their cancer. In these transplants, chemotherapy and total-body radiotherapy ('conditioning') are used to kill residual leukemia cells and the patient's normal blood cells, especially immune cells that could reject the donor cells. Following the chemo/radiotherapy, blood stem cells from the donor are infused. These stem cells will grow and eventually replace the patient's original blood system, including red cells that carry oxygen to our tissues, platelets that stop bleeding from damaged vessels, and multiple types of immune-system white blood cells that fight infections. Mature donor immune cells, especially a type of immune cell called T lymphocytes (or T cells) are transferred along with these blood-forming stem cells. T cells are a major part of the curative power of transplantation because they can attack leukemia cells that have survived the chemo/radiation therapy and also help to fight infections after transplantation. However, donor T cells can also attack a patient's healthy tissues in an often-dangerous condition known as Graft-Versus-Host-Disease (GVHD). Drugs that suppress immune cells are used to decrease the severity of GVHD; however, they are incompletely effective and prolonged immunosuppression used to prevent and treat GVHD significantly increases the risk of serious infections. Removing all donor T cells from the transplant graft can prevent GVHD, but doing so also profoundly delays infection-fighting immune reconstitution and eliminates the possibility that donor immune cells will kill residual leukemia cells. Work in animal models found that depleting a type of T cell, called naïve T cells or T cells that have never responded to an infection, can diminish GVHD while at least in part preserving some of the benefits of donor T cells including resistance to infection and the ability to kill leukemia cells. This clinical trial studies how well the selective removal of naïve T cells works in preventing GVHD after peripheral blood stem cell transplants. This study will include patients conditioned with high or medium intensity chemo/radiotherapy who can receive donor grafts from related or unrelated donors.

Conditions

• Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Acute Biphenotypic Leukemia
• Acute Leukemia of Ambiguous Lineage
• Acute Undifferentiated Leukemia
• Allogeneic Hematopoietic Stem Cell Transplant Recipient
• Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Blastic Plasmacytoid Dendritic Cell Neoplasm
• Childhood Acute Lymphoblastic Leukemia in Remission
• Childhood Acute Myeloid Leukemia in Remission
• Donor
• Lymphoblastic Lymphoma
• Myelodysplastic Syndrome With Excess Blasts
• Myelodysplastic Syndrome With Excess Blasts-1
• Myelodysplastic Syndrome With Excess Blasts-2
• Recurrent Acute Lymphoblastic Leukemia
• Recurrent Acute Myeloid Leukemia
• Recurrent Childhood Acute Lymphoblastic Leukemia
• Recurrent Childhood Acute Myeloid Leukemia
• Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive
• Refractory Acute Lymphoblastic Leukemia
• Refractory Acute Myeloid Leukemia
• Acute Lymphoblastic Leukemia in Remission
• Acute Myeloid Leukemia in Remission

Interventions

PROCEDURE

Allogeneic Hematopoietic Stem Cell Transplantation

Undergo allogeneic HSCT

DRUG

Cyclophosphamide

Given IV

DRUG

Fludarabine Phosphate

Given IV

OTHER

Laboratory Biomarker Analysis

Correlative studies

DRUG

Methotrexate

Given IV

DRUG

Mycophenolate Mofetil

Given IV and PO

PROCEDURE

Peripheral Blood Stem Cell Transplantation

Undergo PBSCT with GCSF-mobilized CD34-enriched PBSC

PROCEDURE

Peripheral Blood Stem Cell Transplantation

Undergo PBSCT with CD45RA-depleted cells

DRUG

Tacrolimus

Given IV or PO

DRUG

Thiotepa

Given IV

RADIATION

Total-Body Irradiation

Undergo TBI

Sponsors & Collaborators

• National Cancer Institute (NCI)

  collaborator NIH

• National Heart, Lung, and Blood Institute (NHLBI)

  collaborator NIH

• Fred Hutchinson Cancer Center

  lead OTHER

Principal Investigators

• Marie Bleakley · Fred Hutch/University of Washington Cancer Consortium

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Max Age

60 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2015-02-03

Primary Completion

2025-04-01

Completion

2025-05-01

FDA Drug

Yes

Countries

• United States

Study Locations