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 | Recruiting Phase 1 DMC FDA Drug FDA Device

• 2 other identifiers: HAPALLNCI-2025-08364
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Relapsed Pediatric ALL; Hematologic Malignancy; Hematopoietic Cell Transplantation

Keywords

Relapsed/Refractory ALL

Outcome Measures

Primary Outcomes (2)

• 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.

  The primary analysis will compute the sample proportions and corresponding binomial exact 95% confidence intervals among evaluable patients for the following toxicities (separately for each toxicity) within 100 days post-HCT: 1) Severe aGVHD defined as Grade 3-4 aGVHD 2) Severe CRS defined as Grade 4 CRS that does not resolve to grade 3 or lower within 72 hours of onset 3) Severe ICANS defined as Grade 4 ICANS that does not resolve to grade 3 or lower within 72 hours of onset 4) TRM defined as death without prior relapse or disease progression within 100 days post-HCT 5) Other toxicity data will also be reported for a complete safety assessment of the study regimen.

  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 measured by the failure to receive CD19-CAR(Mem) T cells among patients who received HCT. The number of patients who fail to receive addback will be reported as the proportion who were unable to receive addback within 60 days post-HCT

  This will be assessed in the first 60 days post-HCT

Secondary Outcomes (6)

• 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

• Estimate 1-year post-transplant relapse free survival

  This will be assessed in the first 3 years post-HCT

• Estimate cumulative incidence of neutrophil engraftment

  This will be assessed in the first 30 days post-HCT

• Estimate cumulative incidence of platelet engraftment

  This will be assessed in the first 100 days post-HCT

• Estimate cumulative incidence of acute and chronic GVHD

  This will be assessed in the first 3 years post-HCT

Study Arms (1)

HAPALL Treatment

EXPERIMENTAL

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

Drug: Anti-Thymocyte Globulin (Rabbit); Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Thiotepa; Drug: Mesna; Drug: Melphalan; Drug: Filgrastim; Device: CliniMACS System

Interventions

Anti-Thymocyte Globulin (Rabbit) DRUG

Days -10, -11, -12.

HAPALL Treatment

Cyclophosphamide DRUG

60 mg/kg intravenous once daily on day -9.

HAPALL Treatment

Fludarabine DRUG

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.

HAPALL Treatment

Thiotepa DRUG

5 mg/kg intravenous twice daily on day -3.

HAPALL Treatment

Mesna DRUG

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.

HAPALL Treatment

Melphalan DRUG

70 mg/m2 intravenous once daily for \>10 kg, 2.3 mg/kg intravenous once daily for ≤10 kg on days -1, and -2.

HAPALL Treatment

Filgrastim DRUG

G-CSF\* 10 mcg/kg/day SC days 0, -1, -2, -3, -4, -5.

Also known as: G-CSF

HAPALL Treatment

CliniMACS System DEVICE

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.

HAPALL Treatment

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hematologic Neoplasms; Recurrence

Interventions

Antilymphocyte Serum; Cyclophosphamide; fludarabine; Thiotepa; Mesna; Melphalan; Filgrastim; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Neoplasms by Site; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Immune Sera; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Biological Products; Complex Mixtures; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Triethylenephosphoramide; Aziridines; Azirines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Biological Factors

Study Officials

• Swati Naik, MBBS

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Swati Naik, MBBS

CONTACT

8662785833; referralinfo@stjude.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2025
• First Posted: December 2, 2025
• Study Start (Estimated): June 3, 2026
• Primary Completion (Estimated): December 1, 2031
• Study Completion (Estimated): December 1, 2035
• Last Updated: April 13, 2026

Record last verified: 2026-04

Locations

US (1)