CD45RA-depleted CD19-CAR T Cell Consolidation After TCRαβ+/CD19 B Cell-depleted Haploidentical Hematopoietic Cell Transplantation for Relapsed/Refractory CD19+ ALL and Lymphoma
St. Jude Children's Research Hospital
60 participants
Mar 3, 2026
INTERVENTIONAL
Conditions
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
Inclusion Criteria20
- 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 Criteria11
- 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
Interventions
Days -10, -11, -12.
60 mg/kg intravenous once daily on day -9.
30 mg/m2 intravenous once daily for \>10 kg, 1 mg/kg intravenous once daily for ≤10 kg on days -4, -5, -6, -7, -8.
5 mg/kg intravenous twice daily on day -3.
Mesna is planned to be administered at 15 mg/kg/dose prior to cyclophosphamide and at approximately 3, 6, and 9 hours after the cyclophosphamide infusion, to give a 1:1 ratio of mesna:cyclophosphamide.
70 mg/m2 intravenous once daily for \>10 kg, 2.3 mg/kg intravenous once daily for ≤10 kg on days -1, and -2.
G-CSF\* 10 mcg/kg/day SC days 0, -1, -2, -3, -4, -5.
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.
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07257419