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

NCT07052370 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: HAP3HCTNCI-2025-04293
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, prospective clinical trial studying the safety and feasibility of providing early memory T-cell DLI. The primary objective is: \- To assess the safety and feasibility of early CD45RA-depleted DLI administration. The secondary objectives are

• To assess the safety and feasibility of the addition of blinatumomab in the early post-transplant period in patients with CD19+ malignancy.
• To measure and describe the pharmacokinetics of rabbit ATG in HCT recipients on this study.

Conditions

Hematologic Malignancy

Keywords

Hematopoietic Cell Transplant

Outcome Measures

Primary Outcomes (1)

• Number of participants experiencing grade 3-4 GVHD and/or transplant related mortality (TRM).

  Safety will be measured by monitoring for the incidence of grade 3-4 GVHD as well as any transplant related mortality experience. Feasibility monitoring will include 1) failure to receive protocol directed DLI among the evaluable participants; and 2) the number of days from transplant infusion to DLI infusion among evaluable participants.

  Within 100 days post-transplant infusion

Secondary Outcomes (2)

• Number of participants experiencing safety issues or feasibility concerns related to blinatumomab administration.

  Within 180 days post-transplant infusion

• Describing pharmacokinetics of rabbit ATG in participants.

  Within 14 days post-transplant infusion

Study Arms (1)

HAP3HCT Treatment

EXPERIMENTAL

Prior to the infusion of donor cells, a preparative regimen consisting of antibodies and chemotherapy will be given. The preparative regimen includes the following total dosages: ATG 5mg/kg (over days -12 to -10); Cyclophosphamide 60 mg/kg (day -9); Fludarabine 150 mg/m2 (over days -8 to -4); Thiotepa 10 mg/kg (divided in two doses on day -3); Melphalan 70 mg/m2 (over days -2 to -1). Following this regimen the TCRαβ-depleted haploidentical donor product will be given on day 0 (subsequent infusion given on day +1 if needed to achieve goal CD34+ cell dose. Approximately 2 weeks later the memory cell donor lymphocyte infusion (DLI) will be given at a dose previously determined to be safe and effective. Blinatumomab will be empirically added for patients with CD19+ malignancy and given at least four weeks after the memory cell DLI.

Drug: Thymoglobulin; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Thiotepa; Drug: Melphalan; Drug: Mesna; Drug: Filgrastim; Drug: Blinatumomab; Device: CliniMACS

Interventions

Thymoglobulin DRUG

IV

HAP3HCT Treatment

Cyclophosphamide DRUG

IV

HAP3HCT Treatment

Fludarabine DRUG

IV

HAP3HCT Treatment

Thiotepa DRUG

IV

HAP3HCT Treatment

Melphalan DRUG

IV

HAP3HCT Treatment

Mesna DRUG

IV

HAP3HCT Treatment

Filgrastim DRUG

IV

HAP3HCT Treatment

Blinatumomab DRUG

IV

HAP3HCT Treatment

CliniMACS DEVICE

The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest.

HAP3HCT Treatment

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Recipient:
• Age less than or equal to 21 years
• High risk hematologic malignancy whereas allogeneic transplantation is the current standard of care. This includes (but is not limited to):
• High risk ALL in CR1 or CR2,
• any ALL in CR3 or subsequent;
• AML in high risk CR1 (AML diagnosis includes myeloid sarcoma),
• any AML in CR2 or subsequent,
• any therapy related AML;
• MDS (primary or secondary),
• NK cell, biphenotypic, or undifferentiated leukemia/lymphoma in CR1 or subsequent;
• CML in accelerated phase, or in chronic phase with persistent molecular positivity or intolerance to tyrosine kinase inhibitor, or a history of blast crisis.
• If prior CNS leukemia, it must be treated and in CNS CR
• Left ventricular ejection fraction \> 40%, or shortening fraction ≥ 25%
• Creatinine clearance (CrCl) or glomerular filtration rate (GFR) ≥ 50 ml/min/1.73m2
• Forced vital capacity (FVC) ≥ 50% of predicted value; or pulse oximetry ≥ 92% on room air if patient is unable to perform pulmonary function testing

You may not qualify if:

• Recipient:
• Has a suitable HLA-identical sibling or suitable 12/12 (HLA-A, B, C, DRB1, DQB1, and DPB1) HLA-matched unrelated donor available in an appropriate time frame.
• Any other active malignancy other than the one for which this HCT is indicated
• Received a prior allogeneic HCT at any time
• Received an autologous HCT within the previous 6 months
• Pregnant, if female is of childbearing potential, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment
• Breast feeding
• Any current uncontrolled bacterial, fungal or viral infection
• Donor:
• Pregnant, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment if female
• If female, breast feeding

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

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

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

thymoglobulin; Cyclophosphamide; fludarabine; Thiotepa; Melphalan; Mesna; Filgrastim; blinatumomab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

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; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Granulocyte Colony-Stimulating Factor; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Proteins; Biological Factors

Study Officials

• Brandon Triplett, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brandon Triplett, MD

CONTACT

8662785833; referralinfo@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2025
• First Posted: July 4, 2025
• Study Start: September 25, 2025
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2030
• Last Updated: December 31, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be made available at the time of article publication.
• Access Criteria: Data will be provided to researchers following a formal request with the following information: full name of requestor, affiliation, data set requested, and timing of when data is needed. As an informational point, the lead statistician and study principal investigator will be informed that primary results datasets have been requested.

Locations

US (1)