RecruitingRecruiting
CD45RA-depleted CD19-CAR T Cell Consolidation After TCRαβ+/CD19 B Cell-depleted Haploidentical Hematopoietic Cell Transplantation for Relapsed/Refractory CD19+ ALL and Lymphoma
NCT07257419 · St. Jude Children's Research Hospital
In plain English
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About this study
This is a Phase I study evaluating the addback of CD19-CAR(Mem) T cells after TCRαβ+/CD19 B cell depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies.
Donors that meet eligibility criteria will be consented to undergo two separate collections: 1) G-CSF mobilized stem cell graft via apheresis for progenitor cell infusion and 2) Non-mobilized peripheral blood mononuclear cells (PBMC) via apheresis for subsequent CAR T-cell manufacturing and DLI if needed.
Patients that meet eligibility criteria to receive therapy will be consented to proceed on study. Treatment will include a conditioning chemotherapy preparative regimen followed by infusion of TCRαβ/CD19 B cell depleted progenitor cell infusion on day 0. Then as early as day + 14 patients will receive the previously manufactured CD19-CAR(Mem) T cell product. Patients will then be monitored for safety and efficacy of the infused CAR T-cell product, as well as collection of correlative samples.
Eligibility criteria
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
Study design
Enrollment target: 70 participants
Allocation: na
Masking: none
Age groups: child, adult
Timeline
Starts: 2026-08-03
Estimated completion: 2035-12
Last updated: 2026-07-17
Interventions
Drug: Anti-Thymocyte Globulin (Rabbit)Drug: CyclophosphamideDrug: FludarabineDrug: ThiotepaDrug: MesnaDrug: MelphalanDrug: FilgrastimDevice: CliniMACS System
Primary outcomes
- • To assess the safety of combining CD19-CAR(Mem) T cells after TCRαβ+/CD19 depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies. (This will be assessed 100 days post-HCT)
- • To assess the 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. (This will be assessed in the first 60 days post-HCT)
Sponsor
St. Jude Children's Research Hospital · other
Contacts & investigators
ContactSwati Naik, MBBS · contact · referralinfo@stjude.org · 888-226-4343
InvestigatorSwati Naik, MBBS · principal_investigator, St. Jude Children's Research Hospital
All locations (1)
St. Jude Children's Research HospitalRecruiting
Memphis, Tennessee, United States