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

St. Jude Children's Research Hospital

Status and phase

Not yet enrolling

Phase 1

Conditions

Hematologic Malignancy

Relapsed Pediatric ALL

Hematopoietic Cell Transplantation

Treatments

Drug: Anti-Thymocyte Globulin (Rabbit)

Drug: Filgrastim

Drug: Thiotepa

Drug: Mesna

Device: CliniMACS System

Drug: Melphalan

Drug: Fludarabine

Drug: Cyclophosphamide

Study type

Interventional

Funder types

Other

Identifiers

NCT07257419

NCI-2025-08364 (Other Identifier)

HAPALL

Details and patient eligibility

About

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+ depleted haploidentical donor transplantation for pediatric patients with relapsed/refractory CD19+ B-cell malignancies.

Secondary Objectives:

To estimate 1-year post-transplant overall survival, relapse 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.

Full description

This is a Phase I study evaluating the addback of CD19-CAR(Mem) T cells after TCRαβ+ 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 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.

Enrollment

60 estimated patients

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

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
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 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

60 participants in 1 patient group

HAPALL Treatment

Experimental group

Description:

Patients receive a conditioning regimen that will comprise of ATG, Fludarabine, Cyclophosphamide. Melphalan and Thiotepa. Following the conditioning regimen, patients receive infusion of TCRαβ 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, Cells for infusion are prepared using the CliniMACS system.

Treatment: