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

NCT ID: NCT07257419

Last Updated: 2025-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-12-31

Study Completion Date

2034-12-31

Brief Summary

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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.

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Detailed Description

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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.

Conditions

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Relapsed Pediatric ALL Hematopoietic Cell Transplantation Hematologic Malignancy

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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HAPALL Treatment

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.

Group Type EXPERIMENTAL

Anti-Thymocyte Globulin (Rabbit)

Intervention Type DRUG

Days -10, -11, -12.

Cyclophosphamide

Intervention Type DRUG

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

Fludarabine

Intervention Type 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.

Thiotepa

Intervention Type DRUG

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

Mesna

Intervention Type 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.

Melphalan

Intervention Type 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.

Filgrastim

Intervention Type DRUG

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

CliniMACS System

Intervention Type 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.

Interventions

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Anti-Thymocyte Globulin (Rabbit)

Days -10, -11, -12.

Intervention Type DRUG

Cyclophosphamide

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

Intervention Type DRUG

Fludarabine

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.

Intervention Type DRUG

Thiotepa

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

Intervention Type DRUG

Mesna

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.

Intervention Type DRUG

Melphalan

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

Intervention Type DRUG

Filgrastim

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

Intervention Type DRUG

CliniMACS System

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.

Intervention Type DEVICE

Other Intervention Names

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G-CSF

Eligibility Criteria

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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
Maximum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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St. Jude Children's Research Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Swati Naik, MBBS

Role: PRINCIPAL_INVESTIGATOR

St. Jude Children's Research Hospital

Locations

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St. Jude Children's Research Hospital

Memphis, Tennessee, United States

Site Status

Countries

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United States

Central Contacts

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Swati Naik, MBBS

Role: CONTACT

8662785833

Facility Contacts

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Swati Naik, MBBS

Role: primary

866-278-5833

Related Links

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http://www.stjude.org

St. Jude Children's Research Hospital

http://www.stjude.org/protocols

Clinical Trials Open at St. Jude

Other Identifiers

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NCI-2025-08364

Identifier Type: OTHER

Identifier Source: secondary_id

HAPALL

Identifier Type: -

Identifier Source: org_study_id

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