TCRαβ-depleted Progenitor Cell Graft With Additional Memory T-cell DLI, Plus Selected Use of Blinatumomab, in Naive T-cell Depleted Haploidentical Donor Hematopoietc Cell Transplantation for Hematologic Malignancies

Summary

Patients less than or equal to 21 years old with high-risk hematologic malignancies who would likely benefit from allogeneic hematopoietic cell transplantation (HCT). Patients with a suitable HLA matched sibling or unrelated donor identified will be eligible for participation ONLY if the donor is not available in the necessary time.

The purpose of the study is to learn more about the effects (good and bad) of transplanting blood cells donated by a family member, and that have been modified in a laboratory to remove the type of T cells known to cause graft-vs.-host disease, to children and young adults with a high risk cancer that is in remission but is at high risk of relapse. This study will give donor cells that have been TCRαβ-depleted. The TCR (T-cell receptor) is a molecule that is found only on T cells. These T-cell receptors are made up of two proteins that are linked together. About 95% of all T-cells have a TCR that is composed of an alpha protein linked to a beta protein, and these will be removed. This leaves only the T cells that have a TCR made up of a gamma protein linked to a delta protein. This donor cell infusion will be followed by an additional infusion of donor memory cells (CD45RA-depleted) after donor cell engraftment.

This study will be testing the safety and effects of the chemotherapy and the donor blood cell infusions on the transplant recipient's disease and overall survival.

Conditions

• Acute Lymphoblastic Leukemia (ALL)
• Acute Myeloid Leukemia (AML)
• Myelodysplastic Syndromes (MDS)
• NK-Cell Leukemia
• Hodgkin Lymphoma
• Non Hodgkin Lymphoma (NHL)
• Juvenile Myelomonocytic Leukemia (JMML)
• Chronic Myeloid Leukemia (CML)

Interventions

DRUG

Cyclophosphamide

Cyclophosphamide is a nitrogen mustard derivative. It acts as an alkylating agent that causes cross-linking of DNA strands by binding with nucleic acids and other intracellular structures, thus interfering with the normal function of DNA. intravenously (IV) once daily (QD) on day -9

BIOLOGICAL

Fludarabine

Fludarabine phosphate is a synthetic purine nucleoside analog. It acts by inhibiting DNA polymerase, ribonucleotide reductase and DNA primase by competing with the physiologic substrate, deoxyadenosine triphosphate, resulting in inhibition of DNA synthesis. fludarabine phosphate IV QD on days -8 to -4

DRUG

Thiotepa

Thiotepa is a cell-cycle nonspecific polyfunctional alkylating agent.

DRUG

Melphalan

Melphalan, a derivative of nitrogen mustard, is a bifunctional alkylating agent. Melphalan is active against tumor cells that are actively dividing or at rest. melphalan IV QD on days -2 to -1

BIOLOGICAL

G-csf

G-csf (granulocytic colony stimulating factor), is a biosynthetic hematopoietic agent that is made using recombinant DNA technology in cultures of Escherichia coli. G-CSF stimulates production, maturation and activation of neutrophils. In addition, endogenous G-CSF enhances certain functions of mature neutrophils, including phagocytosis, chemotaxis and antibody--dependent cellular cytotoxicity.

DRUG

Mesna

Mesna is a synthetic sulfhydryl (thiol) compound. Mesna contains free sulfhydryl groups that interact chemically with urotoxic metabolites of oxaza-phosphorine derivatives such as cyclophosphamide and ifosfamide. Following glomerular filtration, mesna disulfide is rapidly reduced in the renal tubules back to mesna, the active form of the drug.

DEVICE

CliniMACS

Cells for infusion are prepared using the CliniMACS

BIOLOGICAL

ATG (rabbit)

Anti-thymocyte globulin is a purified, pasteurized, gamma immune globulin, obtained by immunization of rabbits with human thymocytes. rabbit anti-thymocyte globulin IV daily over 6 hours on days -5 to -3,

DRUG

Blinatumomab

Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that mediates formation of a synapse between T cells and the CD19+ target cell, resulting in lysis of that CD19+ cell.Blinatumomab will be given to patients with a history of CD19+ malignancy as determined by St. Jude hematopathologist review of current and historical specimens and reports. blinatumomab IV for 28 days beginning at least 1 week post-DLI

BIOLOGICAL

TCRα/β+

IV on day 0 and may receive an additional dose on day 1

BIOLOGICAL

CD19+

IV on day 0 and may receive an additional dose on day 1

BIOLOGICAL

CD45RA-depleted DLI

infusion IV

Sponsors & Collaborators

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Brandon Triplett, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-01-31

Primary Completion

2024-08-07

Completion

2026-06-07

FDA Drug

Yes

FDA Device

Yes

Countries

• United States

Study Locations