Study of huCART19 for Very High-Risk (VHR) Subsets of Pediatric B-ALL

NCT03792633 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 83191618CT014
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase 2 study to evaluate humanized CD19 redirected autologous T cells (or huCART19 cells) with CD19 expressing relapsed and refractory B-cell acute lymphoblastic leukemia. This study is targeting pediatric and young adult patients aged 3 months - 29 years with CD19+ B cell malignancies in newly diagnosed B-ALL patients predicted to have an exceedingly poor outcome with conventional chemotherapy, in high-risk first relapse, or and in second or greater relapse in this phase 2 trial. In addition, a second cohort will test the efficacy of huCART19 in patients with poor response to prior B cell directed engineered cell therapy.

Conditions

Acute Lymphoblastic Leukemia

Outcome Measures

Primary Outcomes (2)

• Number of Subjects With Event-Free Survival in Patients With Newly Diagnosed VHR B-ALL or High-risk Relapse of B-ALL 1 Year After Treatment.

  Time from infusion to the first of event or censoring Events = Relapse, No Response, or Death; Censoring =Initiation of New Anticancer Therapy, Last Day of Follow-up/EOS; whichever occurs first.

  1 year

• Number of Subjects With Event-Free Survival in Patients With Poor Response to Prior B Cell Directed Engineered Cell Therapy 1 Year After Treatment.

  Time from infusion to the first of event or censoring Events = Relapse, No Response (including CR/CRi without B Cell Aplasia), or Death; Censoring =Initiation of New Anticancer Therapy, Last Day of Follow-up/EOS; whichever occurs first.

  1 year

Secondary Outcomes (3)

• Overall Remission Rate

  28 Days

• Overall Remission Rate (Cohort B)

  28 Days

• Percentage of Subjects With Relapse-free Survival

  1 year

Study Arms (2)

Newly Diagnosed VHR B-ALL or High-Risk Relapse of B

EXPERIMENTAL

Biological: huCART19

Poor Response to Prior B Cell Directed Engineered cell therapy

EXPERIMENTAL

Biological: huCART19

Interventions

huCART19 BIOLOGICAL

IV injection

Newly Diagnosed VHR B-ALL or High-Risk Relapse of B; Poor Response to Prior B Cell Directed Engineered cell therapy

Eligibility Criteria

• Age: 3 Months - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Signed informed consent form must be obtained.
• Relapsed or refractory B-cell ALL:
• a. Cohort A: Patients with newly diagnosed VHR B-ALL or high-risk relapse of B-ALL who meet one of the following criteria:
• i. Newly diagnosed NCI HR B-ALL with induction failure: M3 marrow (\>25% blasts) at end of induction OR
• ii. First marrow relapse of B-ALL at \< 36 months from diagnosis OR iii. 2nd or greater relapse OR
• iv. Any relapse after allogeneic HSCT and ≥ 4 months from SCT at enrollment OR
• v. Refractory disease defined as having not achieved an MRD-negative and/or CSF-negative CR after ≥ 2 chemotherapy regimens/cycles of frontline therapy or 1 cycle of reinduction therapy for patients in first relapse OR
• vi. Ineligible for allogeneic SCT because of:
• Comorbid disease
• Other contraindications to allogeneic SCT conditioning regimen
• Lack of suitable donor
• Prior SCT
• Declines allogeneic SCT as the therapeutic option after documented discussion, with expected outcomes, about the role of SCT with a BMT physician not part of the study team b. Cohort B: Patients previously treated with B cell directed engineered cell therapy who meet one of the following criteria: i. partial response or no response to prior cell therapy ii. CD19+ relapse after prior cell therapy iii. demonstrated early (≤6 months from infusion) B cell recovery suggesting loss of engineered cells c. Patients with prior or current history of CNS3 disease will be eligible if CNS disease is responsive to therapy (at infusion, must meet criteria in Section 5.3 of the protocol)
• \. Documentation of CD19 tumor expression in bone marrow, peripheral blood, CSF, or tumor tissue by flow cytometry at relapse (or a recent sample in the case of refractory disease). If the patient has received CD19-directed therapy, then the flow cytometry should be obtained after this therapy to show CD19 expression.
• \. Adequate organ function defined as:

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.
• CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity.
• Pregnant or nursing (lactating) women.
• Uncontrolled active infection.
• Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS or neurotoxicity.

Sponsors & Collaborators

• University of Pennsylvania: lead
• Children's Hospital of Philadelphia: collaborator

Study Sites (1)

Children's Hospital of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

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

Results Point of Contact

• Title: Regulatory Lead
• Organization: University of Pennsylvania

psom-ind-ide@pobox.upenn.edu

215-662-4484

Study Officials

• Shannon Maude, MD, PhD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 2, 2019
• First Posted: January 3, 2019
• Study Start: January 18, 2019
• Primary Completion: April 4, 2024
• Study Completion: April 4, 2024
• Last Updated: June 5, 2025
• Results First Posted: May 16, 2025

Record last verified: 2025-05

Locations

US (1)