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

Phase 1

Recruiting

• Conditions: B-cell Non Hodgkin Lymphoma; B-cell Acute Lymphoblastic Leukemia
• Interventions: Drug: CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells

• Registration Number: NCT04544592
• Lead Sponsor: University of Colorado, Denver

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.

Detailed Description

Pediatric patients with refractory or multiply relapsed leukemia and lymphoma do very poorly with traditional chemotherapy and have overall survival rates of well under 20%. There has been much excitement over the development of Car T cell therapy for these types of leukemia/lymphoma, but many patients may not fit the standard criteria to receive them or they cannot tolerate the extended wait and ongoing therapy that is needed for manufacture of these cells at the commercial level. With this study, the investigators will investigate a new CD19 directed CAR-T therapy that will be manufactured locally with a goal of wider patient inclusion and less delay to CAR-T infusion. The investigators hypothesize that CD19 directed CAR-T cells manufactured using the Prodigy ClinicMACS system developed by Miltenyi (UCD19 CAR-T) will be safe and tolerable and show preliminary efficacy in pediatric patients with relapsed and/or refractory B-ALL or B- NHL.

Study Timeline

• Study First Submitted: 2019-05-29
• Study First Submitted QC: 2020-09-03
• Study First Posted: 2020-09-10
• Study Start: 2021-02-24
• Status Verified: 2024-11
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-06
• Primary Completion: 2026-06
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

1. Meets criteria for potential leukapheresis collection or has leukapheresis product previously collected and stored per recommended guidelines;

2. 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);

3. Willingness to participate in long-term follow-up study;

4. Stated willingness to comply with all study procedures and be available for the duration of the study;

5. Males OR non-pregnant, non-lactating females;

6. Aged 31 days to 30 years (inclusive) at time of consent and enrollment;

7. 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 ;
   • 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.

   • Non-Hodgkin Lymphoma includes all of the following:

   Diffuse large B-cell lymphoma (DLBCL) Burkitt Lymphoma Intermediate lymphoma between Burkitt and DLBCL Primary Mediastinal B-cell Lymphoma (PMBL) Follicular lymphoma High-grade B cell lymphoma Transformed lymphoma

8. Performance score (Lansky or Karnofsky) of 50% or better;

9. Unable to receive commercially available CD19 CAR-T Therapy.

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Exclusion Criteria

1. Active, uncontrolled CNS leukemia or lymphoma, as clinically indicated, at eligibility, prior to lymphodepleting chemotherapy (LD chemo), and pre-cell infusion;

2. Active Graft-versus-Host Disease (GvHD);

3. Active, uncontrolled, life threatening infection that at the determination of the treating physician would preclude safe leukapheresis or tolerance of lymphodepleting chemotherapy, cell infusion, or cytokine release syndrome;

4. Evidence of severe organ dysfunction that at the determination of the treating physician would preclude safe leukapheresis or tolerance of lymphodepleting chemotherapy, cell infusion, or cytokine release syndrome including any of the following:

   • Myocardial dysfunction (based on age standards)
   • Baseline oxygen saturation of < 90% on room air
   • Diffusion capacity of the lungs for carbon monoxide (DLCO) < 40%, as determined within 45 days before cell infusion
   • 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)

5. Post-pubertal females that are pregnant, planning to become pregnant, or unwilling to use birth control (includes abstinence) for the study duration;

6. Known HIV infection, or active Hepatitis B or active Hepatitis C infection;

7. Prior gene therapy, including prior CAR-T cell.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
II: Dose Expansion	CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells	22-40 additional subjects treated at the RP2D, including those treated within the phase 1 portion of the trial.
I: Dose Escalation	CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells	First 3-21 subjects enrolled. Treated with escalating doses of therapy until the RP2D is determined.

Primary Outcome Measures

Name	Time	Method
Dose limiting toxicities	Up to 21 months	Adverse events (toxicity assessments) will be done by medical staff at different time points

Secondary Outcome Measures

Name	Time	Method
Overall Survival	5 years	The subject will be followed throughout the study and up to 5 years after the study for overall survival.
Non-Relapse Mortality	5 years	The subject will be followed throughout the study and up to 15 years after the study for non-relapse mortality
Relapse	5 years	The subject will be followed throughout the study and up to 15 years after the study for relapse.
Time to Transplant	5 years	The subject will be followed throughout the study and up to 5 years after the study for time to transplant.

Trial Locations

Locations (1)

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States