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CD45RA-depleted CD19-CAR T Cell Consolidation After TCRαβ+/CD19 B Cell-depleted Haploidentical Hematopoietic Cell Transplantation for Relapsed/Refractory CD19+ ALL and Lymphoma

RECRUITINGPhase 1Sponsored by St. Jude Children's Research Hospital
Actively Recruiting
PhasePhase 1
SponsorSt. Jude Children's Research Hospital
Started2026-03-03
Est. completion2031-12
Eligibility
Healthy vol.Accepted
Locations1 site

Summary

The purpose of this study is to learn more about newer methods of transplanting blood cells donated by a partially matched family member to children with high-risk CD19 positive leukemia ALL. Primary Objective: \- To assess the safety and feasibility of combining CD19-CAR(Mem) T cells after TCRαβ+/CD19 depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies. Secondary Objectives: * To estimate 1-year post-transplant overall survival, event-free survival, and GVHD-free relapse-free survival (GRFS). * To estimate cumulative incidence of engraftment, acute and chronic GVHD, and immune-related adverse events, including CRS and ICANS.

Eligibility

Healthy volunteers accepted
Inclusion Criteria:

Recipient

* Age less than or equal to 21 years
* High risk hematologic malignancy where allogeneic transplantation is the current standard of care. This includes (but is not limited to):

  * High risk CD19+ B cell ALL in CR1 or CR2
  * Any CD19+ B-cell ALL in CR3 or subsequent
* 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
* If sexually active, agreement to use birth control until 2 weeks after completion of the mobilization and apheresis procedure
* 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
* Pregnant, if female is of childbearing potential, negative test must be confirmed by serum or urine pregnancy test within 14 days prior to enrollment
* If sexually active, agreement to use birth control until 6 months after T cell infusion
* Breast feeding
* Any severe 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

Conditions4

CancerHematologic MalignancyHematopoietic Cell TransplantationRelapsed Pediatric ALL

Interventions7

Locations1 site

St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
Swati Naik, MBBS866-278-5833referralinfo@stjude.org

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