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

NCT03849651 | Active Not Recruiting Phase 2 Results FDA Drug FDA Device

• 2 other identifiers: HAP2HCTNCI-2019-00338
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Maximum Effective Dose for Prophylactic CD45RA-depleted DLI

  The maximum effective dose (MED) of CD45RA-depleted DLI, defined as the maximum value of doses that satisfy the proportion of patients with their memory T cell count measured at week 4 post-DLI more than 300/uL is more than 50% and the toxicity of grade 3-4 aGVHD is less than 20%. Dose selection used a protocol-specified algorithm.

  4 weeks post-DLI (up to approximately 12 weeks post-transplant)

• One-year Event Free Survival (EFS) After Completion of the Protocol

  Kaplan-Meier estimate of the percentage of being alive and relapse free one year after the date of transplant. (Events=relapse, death)

  One year after receiving transplant

Secondary Outcomes (6)

• The Number of Patients Experiencing Blinatumomab Permanent Discontinuation Due to Toxicity

  28 days after receiving first dose of Blinatumomab (up to approximately 7 months post-transplant)

• The Estimate of Cumulative Incidence of Relapse

  1 year after receiving transplant]

• The Estimate of Overall Survival

  One year after receiving transplant

• The Cumulative Incidence of Any Severity Chronic Graft-Versus-Host Disease (GVHD)

  One year after receiving transplant

• The Cumulative Incidence of Any Grade Acute Graft-Versus-Host Disease (GVHD)

  One year after receiving transplant

Study Arms (1)

Transplant participants

EXPERIMENTAL

Participants receive a conditioning regimen of ATG (rabbit),Cyclophosphamide 60 mg/kg intravenous once daily, mesna, fludarabine, thiotepa, melphalan, followed by HPC,A Infusion(TCRα/β+ and CD19+ depleted),HPC, A infusion (if needed to achieve goal CD34+ cell dose.CD45RA-depleted DLI will be given at least two weeks after engraftment. Blinatumomab will be given at least one week post-DLI, and only to patients with CD19+ malignancies. G-csf 5mcg/kg subcutaneous or intravenous daily until ANC \>2000 for 2 consecutive days. Cells for infusion are prepared using the CliniMACS system.

Drug: Cyclophosphamide; Biological: Fludarabine; Drug: Thiotepa; Drug: Melphalan; Biological: G-csf; Drug: Mesna; Device: CliniMACS; Biological: ATG (rabbit); Drug: Blinatumomab; Biological: TCRα/β+; Biological: CD19+; Biological: CD45RA-depleted DLI

Interventions

Fludarabine BIOLOGICAL

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

Also known as: Fludara

Transplant participants

CD45RA-depleted DLI BIOLOGICAL

infusion IV

Transplant participants

Cyclophosphamide DRUG

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

Also known as: Cytoxan

Transplant participants

Thiotepa DRUG

Thiotepa is a cell-cycle nonspecific polyfunctional alkylating agent.

Also known as: Thioplex

Transplant participants

Melphalan DRUG

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

Also known as: Alkeran

Transplant participants

G-csf BIOLOGICAL

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.

Also known as: Neupogen, Filgrastim

Transplant participants

Mesna DRUG

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.

Also known as: Mesnex

Transplant participants

CliniMACS DEVICE

Cells for infusion are prepared using the CliniMACS

Also known as: CliniMACS Prodigy

Transplant participants

ATG (rabbit) BIOLOGICAL

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,

Also known as: Thymoglobulin

Transplant participants

Blinatumomab DRUG

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

Also known as: Blincyto

Transplant participants

TCRα/β+ BIOLOGICAL

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

Transplant participants

CD19+ BIOLOGICAL

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

Transplant participants

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age less than or equal to 21 years.
• Does not have a suitable HLA-matched sibling donor (MSD) or volunteer 10/10 HLA-matched unrelated donor (MUD) available in the necessary time for progenitor cell donation.
• Has a suitable single haplotype matched (≥ 3 of 6) family member donor.
• High risk hematologic malignancy. High risk ALL in CR1. Examples include, but not limited to: t(9;22) with persistent or recurrent transcript, hypodiploid cytogenetics, MRD \>1% at the end of induction, M2 or greater marrow at the end of induction, recurrent or rising MRD after induction, Infants with MLL fusion or t(4;11), relapse after prior CART therapy.
• ALL in High risk CR2. Examples include, but not limited to t(9;22), BM relapse \<36 mo CR1 or \<6mo after completion of therapy, any T-ALL, very early (\< 6mo CR1) isolated CNS relapse, late BM relapse with poor response to standard reinduction therapy(e.g. MRD positive or recurrence after two blocks), relapse after prior CART therapy.
• ALL in CR3 or subsequent.
• AML in high risk CR1 (diagnosis of AML includes myeloid sarcoma). Examples include but not limited to: preceding MDS or MDS-related AML, FAB M0, FAB M6, FAB M7 with high risk genetics such as ML not t(1;22), MRD \> 0.1% after two cycles of induction, MRD \> 1% after one cycle of induction, FLT3-ITD in combination with NUP98-NSD1 fusion or WT1 mutation, any high risk cytogenetics such as: DEK-NUP214 \[t(6;9)\], KAT6A-CREBBP \[t(8;16)\], RUNX1-CBFA2T3 \[t(16;21)\], -7, -5, 5q-, KMT2A-MLLT10 \[t(6;11)\], KMT2A-MLLT4 \[t(10;11)\], inv(3)(q21q26.2), CBFA2T3-GLIS2 \[inv(16)(p13.3q24.3)\], NUP98-KDM5A \[t(11;12)(p15;p13)\], ETV6-HLXB \[t(7;12)(q36;p13)\], NUP98-HOXA9 \[t(7;11)(p15.4;p15)\], NUP98-NSD1.
• AML in CR2 or subsequent.
• Therapy related AML, with prior malignancy in CR \> 12mo
• MDS, primary or secondary
• NK cell, biphenotypic, or undifferentiated leukemia in CR1 or subsequent.
• CML in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor.
• Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize progenitor cells for autologous HCT.
• Non-Hodgkin lymphoma in CR2 or subsequent after failure of prior autologous HCT, or unable to mobilize progenitor cells for autologous HCT.
• JMML

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Leukemia, Large Granular Lymphocytic; Hodgkin Disease; Lymphoma, Non-Hodgkin; Leukemia, Myelomonocytic, Juvenile; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Thiotepa; Melphalan; Granulocyte Colony-Stimulating Factor; Filgrastim; Mesna; thymoglobulin; blinatumomab

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Bone Marrow Diseases; Leukemia, T-Cell; Lymphoma; Myelodysplastic-Myeloproliferative Diseases; Myeloproliferative Disorders; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Results Point of Contact

• Title: Brandon Triplett, MD
• Organization: St. Jude Children's Research Hospital

referralinfo@stjude.org

8662785833

Study Officials

• Brandon Triplett, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 20, 2019
• First Posted: February 21, 2019
• Study Start: January 31, 2019
• Primary Completion: August 7, 2024
• Study Completion (Estimated): June 7, 2026
• Last Updated: April 13, 2026
• Results First Posted: March 4, 2026

Record last verified: 2026-03

Locations

US (1)