Autologous HuCART19 T Cells Manufactured Using the CliniMACS Prodigy Platform for Pediatric B-ALL (huCART19 Prodigy)

NCT05480449 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 22-01997822CT011
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

This study will determine the safety and efficacy of moving to a second-generation manufacturing process using the CliniMACS Prodigy platform to manufacture huCART19 cells for patients with B cell Acute Lymphoblastic Leukemia (B-ALL).

Conditions

B Cell Acute Lymphoblastic Leukemia (B-ALL); B Lineage Lymphoblastic Lymphoma

Outcome Measures

Primary Outcomes (2)

• Safety of huCART19 Administration

  The safety of the administering Humanized Cd19-Directed Chimeric Antigen Receptor T-Cells (huCART9) will be measured by the monitoring the frequency and severity of adverse events in patients with advanced or refractory CD19+ hematologic malignancies, including those previously treated with cell therapy.

  5 years

• Efficacy of huCART19 Administration

  The efficacy of huCART9 will be measured by the evaluating the overall response rate in patients with advanced or refractory CD19+ hematologic malignancies, including those previously treated with cell therapy.

  5 years

Secondary Outcomes (8)

• Manufacturing Feasibility

  5 years

• Safety of huCART19 as measured by ≥ Grade 3 toxicity rate

  5 years

• Anti-tumor response due to huCART19 cell infusions

  5 years

• Remission Rate

  5 years

• huCART19 cell persistence

  5 years

Study Arms (2)

Dose Escalation Arm

EXPERIMENTAL

The phase 1 dose escalation portion of the trial will use a standard "3+3" design to establish the recommended phase 2 dose of huCART19 cells in patients with subjects with prior treatment with CD19-directed CAR T cells. Two dose escalations of huCART19 are planned for the dose escalation phase.

Biological: Autologous Humanized CD19-Directed Chimeric Antigen Receptor T-Cells (huCART19)

Dose Expansion Arms

EXPERIMENTAL

If at least one dose level of the dose escalation phase is determined to be safe, the phase 2b dose expansion phase of the trial will be opened to enrollment. Subjects will receive the highest dose of huCART19 cells that were determined to be safe in the dose escalation part of the trial. 2 cohorts are planned: * Cohort A (relapsed/refractory, CAR T cell naïve) * Cohort B (prior treatment with CD19-directed CAR T cells)

Biological: Autologous Humanized CD19-Directed Chimeric Antigen Receptor T-Cells (huCART19)

Interventions

Autologous Humanized CD19-Directed Chimeric Antigen Receptor T-Cells (huCART19) BIOLOGICAL

The investigational agent in this protocol is humanized CART19 cells (huCART19). Autologous T cells will be engineered to express an extracellular single chain antibody (scFv) with specificity for CD19. This will be expected to redirect specificity of the transduced T cells for cells that express CD19, a molecule that is restricted in expression on the surface of the malignant cells and on normal B cells.

Dose Escalation Arm; Dose Expansion Arms

Eligibility Criteria

• Age: 0 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Signed Informed Informed Consent
• Subjects with documented CD19+ ALL or Lly:
• a. Cohort A: Subjects with relapsed or refractory ALL or Lly who have not previously received CAR T-cell Therapy: i. 2nd or greater relapse (marrow or extramedullary) OR ii. Any relapse after allogeneic HSCT and ≥4 months from HSCT at enrollment OR iii. Refractory disease defined as having not achieved an MRD-negative (by multiparameter flow cytometry) or CSF-negative CR after ≥2 chemotherapy regimens/cycles of frontline therapy, or 1 cycle of reinduction therapy for subjects in first relapse OR iv. Newly diagnosed NCI high-risk B-ALL with induction failure, defined as a M3 bone marrow (≥25%) blasts at the end of induction chemotherapy OR v. First bone marrow relapse of B-ALL at \<36 months after initial diagnosis OR vi. First or greater CNS relapse of B-ALL vii. Ineligible for allogeneic HSCT because of at least one of the following:
• \. Comorbid disease 2. Other contraindications to HSCT conditioning regimen 3. Lack of suitable donor 4. Prior HSCT 5. Declines HSCT as the therapeutic option after documented discussion, with expected outcomes, and the role of HSCT with a BMT physician not a part of the study team.
• b. Cohort B: Subjects with poor response to prior B cell directed engineered cell therapy, defined as any one of the following: i. Partial response or no response to prior cell therapy ii. CD19+ relapse after prior cell therapy, defined as bone marrow blasts \> 0.01% by multiparameter flow cytometry or evidence of extramedullary disease iii. Demonstrated early (≤6 months from infusion) B cell recovery suggesting loss of engineered cells
• \. Subjects with prior or current history of CNS3 disease will be eligible if Central Nervous System (CNS) disease is responsive to therapy.
• \. Documentation of CD19 tumor expression in bone marrow, peripheral blood, cerebrospinal fluid (CSF), or tumor tissue by flow cytometry. If the subject has received CD19-directed therapy, flow cytometry should be obtained after this therapy to demonstrate CD19 expression.
• \. Age 0-29 years
• \. Adequate organ function.
• a. Serum creatinine based on age/gender b. Adequate liver function: i. ALT within 5x ULN in the absence of ALL infiltration of the liver ii. Bilirubin ≤3x the upper limit of normal iii. ALT and/or bilirubin results that exceed this range are acceptable if, in the opinion of the physician-investigator (or as confirmed by liver biopsy), the abnormalities are directly related to ALL infiltration of the liver.
• c. Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and \< Grade 3 hypoxia; DLCO ≥ 40% (corrected for anemia if necessary) if PFTs are clinically appropriate as determined by the investigator.
• d. Left Ventricular Shortening Fraction (LVSF) ≥28% or Ejection Fraction (LVEF) ≥45% confirmed by echocardiogram or another scan. In cases where quantitative assessment of LVSF/LVEF is not possible, a statement by the cardiologist that the ECHO shows qualitatively normal ventricular function will suffice.
• \. Adequate performance status defined as Lanksy or Karnofsky performance score ≥50
• \. Subjects of reproductive potential must agree to use acceptable birth control methods.

You may not qualify if:

• Active hepatitis B or active hepatitis C
• HIV infection
• Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy.
• Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician's opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well.
• CNS disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
• Subjects who are pregnant or nursing.
• Uncontrolled active infection.
• History of seizure disorder that requires ongoing anti-epileptic therapy.
• If the subject has received previous CAR T cell therapies, history of grade 3 or higher ICANS following administration of a CAR T cell product.

Sponsors & Collaborators

• Stephan Grupp MD PhD: lead
• Children's Hospital of Philadelphia: collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Allison Barz Leahy, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

• Stephan Grupp, MD,PhD

  Children's Hospital of Philadelphia

  STUDY DIRECTOR

Central Study Contacts

CART Nurse Navigator

CONTACT

445-942-5891; CARTNurseNavigator@chop.edu

Melissa S Varghese, M.S.

CONTACT

8455535358; varghesem@chop.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief, Cell Therapy and Transplant Section Director, Susan S. and Stephen P. Kelly Center for Cancer Immunotherapy Medical Director, Cell and Gene Therapy Lab

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: July 29, 2022
• Study Start: September 20, 2022
• Primary Completion (Estimated): September 20, 2027
• Study Completion (Estimated): September 20, 2029
• Last Updated: December 26, 2025

Record last verified: 2025-12

Locations

US (1)