Evaluation of CD19-Specific CAR Engineered Autologous T-Cells for Treatment of Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia

NCT03573700 | Active Not Recruiting Phase 1 Results FDA Drug FDA Device

• 2 other identifiers: SJCAR19NCI-2017-01399
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

SJCAR19 is a research study seeking to evaluate the use of chimeric antigen receptor (CAR) T cell therapy, a type of cellular therapy, for the treatment of pediatric, adolescent and young adult patients with relapsed or refractory CD19+ acute lymphoblastic leukemia (ALL). CAR therapy combines two of the body's basic disease fighters: antibodies and T Cells. For this type of therapy, peripheral (circulating) immune cells are collected and then undergo a manufacturing process to engineer them to more effectively kill cancer cells. The SJCAR19 product will be manufactured at the St. Jude Children's Research Hospital's Good Manufacturing Practice (GMP) facility. The main purpose of this study is to determine:

1. 1.The largest dose of SJCAR19 that is safe to give,
2. 2.How long SJCAR19 cells last in the body,
3. 3.The side effects of SJCAR19, and
4. 4.Whether or not treatment with SJCAR19 is effective in treating people with refractory or relapsed ALL.

Conditions

Acute Lymphoblastic Leukemia, in Relapse; Acute Lymphoblastic Leukemia, Refractory

Keywords

Leukemia; Leukemia, lymphoid; Leukemia, B-cell; Relapsed; Refractory; Pediatric; Chimeric antigen receptor; CAR; CAR T cell; Anti-CD19; CD19

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose and Dose-limiting Toxicities

  The primary objectives for the Phase I study portion are to determine the maximum tolerated dose (MTD) and characterize the safety profile and dose-limiting toxicities (DLTs) of treatment with SJCAR19 in pediatric and young adult patient's ≤ 21 years of age, with relapsed or refractory CD19+ ALL. The proportion of participants with dose limiting toxicities are reported.

  4 weeks post-SJCAR19 infusion

• Complete Response Rate

  The primary objective for the Phase II study portion is to evaluate the complete response (CR) rates of SJCAR19 in pediatric and young adult patient's ≤ 21 years of age, with relapsed or refractory CD19+ ALL.

  4 weeks post-SJCAR19 infusion

Study Arms (1)

SJCAR19 Therapy

EXPERIMENTAL

Patients in both the Phase I and Phase II portion of the study will receive lymphodepleting chemotherapy (unless determined by PI that lymphodepletion is not necessary), followed by a single infusion of the patient-derived SJCAR19 cellular product. The most commonly used lymphodepleting chemotherapy regimen will consist of the agents: Fludarabine and Cyclophosphamide. They will also receive Mesna. Dosing of SJCAR19 on the Phase I study will follow a dose escalation schema, with dose changes based on dose-limiting toxicities. In the Phase II study, SJCAR19 dosing with follow the maximum tolerated dose, as determined in the Phase I portion. Cells for infusion are prepared using the CliniMACS System.

Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Mesna; Device: CliniMACS; Biological: CD19- specific CAR engineered autologous T-cells (SJCAR19 product)

Interventions

Cyclophosphamide DRUG

Given IV

Also known as: Cytoxan

SJCAR19 Therapy

Fludarabine DRUG

Given IV

Also known as: Fludara

SJCAR19 Therapy

Mesna DRUG

Given IV

Also known as: Mesnex

SJCAR19 Therapy

CliniMACS 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.

SJCAR19 Therapy

CD19- specific CAR engineered autologous T-cells (SJCAR19 product) BIOLOGICAL

Given IV

SJCAR19 Therapy

Eligibility Criteria

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

You may qualify if:

• Age ≤ 21 years old
• CD19+ ALL with any of the following:
• Minimal Residual Disease (MRD) ≥ 1% at end of up-front induction therapy
• Hypodiploid (\< 44 chromosomes or \< 0.95 DNA index) CD19+ ALL with detectable disease at the end of up-front induction therapy
• Increase in disease burden any time after the completion of up-front induction therapy
• Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission
• Refractory disease despite salvage therapy
• st or greater relapse
• Estimated life expectancy of \> 12 weeks
• Karnofsky or Lansky (age-dependent) performance score ≥ 50
• Patients with a history of prior allogeneic hematopoietic cell transplantation \[HCT\] must be clinically recovered from prior HCT therapy, have no evidence of active GVHD and have not received a donor lymphocyte infusion (DLI) within the 28 days prior to apheresis
• For females of child bearing age:
• Not lactating with intent to breastfeed
• Not pregnant with negative serum pregnancy test within 7 days prior to enrollment

You may not qualify if:

• Known primary immunodeficiency
• History of HIV infection
• Severe intercurrent bacterial, viral or fungal infection
• History of hypersensitivity reactions to murine protein-containing products
• Eligibility Criteria for Manufacturing SJCAR19:
• CD19+ ALL with any of the following:
• Primary refractory disease despite at least 2 cycles of an intensive chemotherapy regimen designed to induce remission
• Refractory disease despite salvage therapy
• nd or greater relapse
• Any relapse after allogeneic hematopoietic cell transplantation
• st relapse if patient requires an allogeneic HCT as part of standard of care relapse therapy, but is found to be ineligible and/or unsuitable for HCT
• Age: ≤ 21 years of age
• Karnofsky or Lansky (age-dependent) performance score ≥ 50
• Estimated life expectancy of \> 12 weeks
• Meets eligibility criteria to undergo autologous apheresis, or have previously undergone autologous apheresis

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Publications (1)

• Talleur AC, Qudeimat A, Metais JY, Langfitt D, Mamcarz E, Crawford JC, Huang S, Cheng C, Hurley C, Madden R, Sharma A, Suliman A, Srinivasan A, Velasquez MP, Obeng EA, Willis C, Akel S, Karol SE, Inaba H, Bragg A, Zheng W, Zhou SM, Schell S, Tuggle-Brown M, Cullins D, Patil SL, Li Y, Thomas PG, Zebley C, Youngblood B, Pui CH, Lockey T, Geiger TL, Meagher MM, Triplett BM, Gottschalk S. Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL. Blood Adv. 2022 Nov 8;6(21):5737-5749. doi: 10.1182/bloodadvances.2021006293.

  PMID: 35446934 DERIVED

Related Links

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

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Leukemia, Lymphoid; Leukemia, B-Cell; Recurrence

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Mesna

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Results Point of Contact

• Title: Aimee Talleur, MD
• Organization: St. Jude Children's Research Hospital

referralinfo@stjude.org

8662785833

Study Officials

• Aimee C. Talleur, MD

  St. Jude Children's Research Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

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: June 20, 2018
• First Posted: June 29, 2018
• Study Start: July 24, 2018
• Primary Completion: July 1, 2023
• Study Completion (Estimated): July 1, 2026
• Last Updated: November 18, 2025
• Results First Posted: October 30, 2024

Record last verified: 2025-11

Locations

US (1)