TCRαβ‑depleted haploidentical stem cell graft with early memory T‑cell donor lymphocyte infusions and selective blinatumomab for pediatric and young adult blood cancers

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

This will test whether giving a TCRαβ‑depleted haploidentical stem cell graft plus early CD45RA‑depleted memory T‑cell infusions, with selective use of blinatumomab for CD19+ disease, is safe for children and young adults undergoing transplant for high‑risk blood cancers.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: N/A to 21 Years
• Sex: All
• Sponsor: St. Jude Children's Research Hospital (Academic / other)
• Drugs / interventions: blinatumomab, chemotherapy, Cyclophosphamide, Fludarabine
• Locations: 1 site (Memphis, Tennessee)
• Trial ID: NCT07052370 on ClinicalTrials.gov

What this trial studies

This is a phase I prospective study of patients age ≤21 with high‑risk hematologic malignancies who lack a matched sibling or unrelated donor, receiving a TCRαβ‑depleted haploidentical donor product followed by early CD45RA‑depleted donor lymphocyte infusions. Participants receive a defined preparative regimen including rabbit ATG, cyclophosphamide, fludarabine, thiotepa, and melphalan before graft infusion. Selected patients with CD19+ disease may receive blinatumomab in the early post‑transplant period. The primary goal is to test safety and feasibility of early memory T‑cell DLI and to characterize ATG pharmacokinetics; secondary endpoints include safety of adding blinatumomab and immune/clinical outcomes.

Who should consider this trial

Good fit: Ideal candidates are children and young adults (≤21 years) with high‑risk hematologic malignancies in remission who lack a matched related or unrelated donor and are eligible for allogeneic transplant.

Not a fit: Patients older than 21, those with conditions that preclude transplant (significant organ dysfunction or uncontrolled infection), or those with diseases not eligible under the protocol are unlikely to benefit from this study.

Why it matters

Potential benefit: If successful, this approach could make haploidentical transplants safer for young patients by improving immune recovery and disease control while limiting severe graft‑versus‑host disease.

How similar studies have performed: Prior work with TCRαβ‑depleted haploidentical grafts and memory T‑cell infusions has shown encouraging safety and immune recovery, but the specific early CD45RA‑depleted DLI strategy combined with routine early blinatumomab use is relatively novel and still under early testing.

Eligibility criteria

Inclusion Criteria:

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
* Karnofsky or Lansky (age dependent) performance score ≥ 50 (See APPENDIX A)
* Bilirubin ≤ 3 times the upper limit of normal for age
* Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≤ 5 times the upper limit of normal for age

Donor:

* At least single haplotype matched (≥ 4 of 8) family member
* At least 18 years of age
* HIV negative
* Regarding donation eligibility, is identified as either:

  * Completed the process of donor eligibility determination as outlined in 21 CFR 1271 and agency guidance; OR
  * Does not meet 21 CFR 1271 eligibility requirements, but has a declaration of urgent medical need completed by the principal investigator or physician sub-investigator per 21 CFR 1271

Exclusion Criteria:

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

Where this trial is running

Memphis, Tennessee

• St. Jude Children's Research Hospital — Memphis, Tennessee, United States (Recruiting)

Study contacts

• Principal investigator: Brandon Triplett, MD — St. Jude Children's Research Hospital
• Study coordinator: Brandon Triplett, MD

Conditions Hematologic Malignancy; Hematopoietic Cell Transplant