UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL

NCT04544592 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 18-2424.ccNCI-2020-08490
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial will investigate a new CD19 directed CAR-T therapy manufactured locally with the goals to expedite infusion to wider patient inclusion that includes those who were previously excluded, such as pediatric patients with B-cell NHL and patients in primary relapse.

Conditions

B-cell Acute Lymphoblastic Leukemia; B-cell Non Hodgkin Lymphoma

Keywords

CD19; CAR-T; pediatric; relapsed; refractory; B-ALL; B-NHL; Miltenyi CliniMACS Prodigy

Outcome Measures

Primary Outcomes (2)

• Determine the safety and tolerability of UCD19 CAR-T infusion in pediatric patients with B-ALL or B-NHL

  DLTs of UCD19 CAR-T will be assessed at each of the dose levels in a standard 3+3 dose-escalation design with a determination of recommended Phase 2 dose (RP2D).

  Post UCD19 infusion to Day 28

• Determine the preliminary efficacy of UCD19 CAR-T cells in pediatric patients with B-ALL or B-NHL

  Following determination of UCD19 CAR-T RP2D, there will be a cohort expansion to determine preliminary efficacy and biological activity by assessment of CR status.

  Day 28 (for B-ALL) and Day 90 (for B-NHL) post UCD19 infusion

Secondary Outcomes (9)

• Determine the preliminary efficacy of UCD19 CAR-T cells in pediatric patients with B-ALL during the expansion phase

  Day 60

• Determine the preliminary efficacy of UCD19 CAR-T cells in pediatric patients with B-ALL during the expansion phase

  Day 90

• Determine the preliminary efficacy of UCD19 CAR-T cells in pediatric patients with B-ALL during the expansion phase

  Months 1, 2, 3, 6, and 12

• Determine the preliminary efficacy of UCD19 CAR-T cells in pediatric patients with B-ALL during the expansion phase

  Months 1, 2, 3, 6, and 12

• Determine the preliminary efficacy of UCD19 CAR-T infusion in pediatric patients after first relapse with B-ALL during the expansion phase

  At Months 6 and 12

Study Arms (2)

Phase I: Dose Escalation

EXPERIMENTAL

First 4-18 subjects enrolled. Treated with escalating doses of therapy until the recommended phase 2 dose (RP2D) is determined.

Drug: CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells

Phase II: Dose Expansion

EXPERIMENTAL

Up to 18 additional subjects will be treated at the recommended Phase 2 dose (RP2D) to allow for 12 total subjects to be treated in each cohort, including those treated within the phase 1 portion at the RP2D.

Drug: CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells

Interventions

CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells DRUG

The CD19 CAR used in this study consists of three main components: the variable regions of the anti-CD19 monoclonal antibody FMC63 71, linked to the TNFRSF-19-derived transmembrane domain, the 4-1BB costimulatory molecule, and the signaling domain of the CD3-zeta molecule. The DNA encoding this receptor was cloned into a lentiviral vector (LV) backbone.

Phase I: Dose Escalation; Phase II: Dose Expansion

Eligibility Criteria

• Age: 31 Days - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Meets clinical criteria for leukapheresis or has a leukapheresis product previously collected and stored per recommended guidelines.
• Provision of signed and dated consent form from parent or guardian (patients \<18), the patient themselves (\>18), or legally authorized representative (patient \>18 who lack decision-making capacity); Pediatric patients will be included in age-appropriate discussions and assent will be obtained for those \> 7 years of age, when appropriate, according to institutional standards.
• Willingness to participate in long term follow up study.
• Stated willingness to comply with all study procedures and be available for the duration of the study.
• Males OR non-pregnant, non-breastfeeding females.
• o Patients of child-bearing potential or capable of fathering a child must agree to use highly effective contraception from the time of initial CAR T cell administration though 12 months following the final administration of investigational product.
• Aged 31 days to 30 years (inclusive) at time of consent and enrollment.
• Acute Lymphoblastic Leukemia (ALL) OR Non-Hodgkin Lymphoma (NHL) of B-cell origin that:
• Has confirmed expression of CD19 by flow cytometry, immunohistochemistry (IHC), or both.
• Cohort One Criteria:
• Meets any one of the following conditions:
• Relapsed two or more times
• Relapsed at any time after allogeneic BMT
• Refractory to standard therapy as determined by the treating physician
• Meets criteria for BMT but is ineligible as determined by the treating physician Patient and/or parents declining BMT options and would prefer CAR-T Therapy.

You may not qualify if:

• Evidence of rapidly progressive disease without adequate salvage/bridging regimens as determined by the investigator.
• Active Graft-versus-Host Disease (GvHD).
• Active, uncontrolled, life-threatening infection that at the determination of the treating physician would preclude safe leukapheresis or tolerance of LD chemotherapy, cell infusion, or cytokine release syndrome.
• Evidence of severe organ dysfunction as defined by:
• Myocardial dysfunction: Ejection fraction ≤ 40% or shortening fraction ≤ 28%, evidence of physiologically significant pericardial effusion as determined by an echocardiogram (ECHO), and clinically significant electrocardiogram (ECG) findings.
• Baseline oxygen saturation of ≤ 90% on room air
• Transaminases \> 10x upper limit of normal (ULN) or bilirubin \>2x the ULN, unless thought to be related to primary disease
• Estimated Cr clearance \<60 mL/min/1.73 m2 (if nuclear medicine GFR or other more specific testing exceeds this level than it can supersede the estimated clearance)
• Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration.
• Known HIV infection, or active Hepatitis B or active Hepatitis C infection.

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Children's Hospital Colorado: collaborator

Study Sites (1)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, B-Cell; Recurrence

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Vanessa Fabrizio, MD, MS

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vanessa Fabrizio, MD, MS

CONTACT

720-777-6860; BMT@childrenscolorado.org

Kayla Ortiz

CONTACT

720-777-2564; kayla.ortiz@childrenscolorado.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2019
• First Posted: September 10, 2020
• Study Start: March 10, 2021
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: April 20, 2026

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)