UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age31-30
SponsorUniversity of Colorado, Denver
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Disqualifiers
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.
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.
Trial design
Design model
Sequential
Treatments tested in this trial
CD19CAR-CD3Zeta-4-1BB-Expressing Autologous T-Lymphocyte Cells
DrugThe 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.
Treatment groups
45 Participants
are divided into 2 treatment groupsGroup A: Phase I: Dose EscalationExperimental treatment 1 intervention
Group B: Phase II: Dose ExpansionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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).
Time frame
Post UCD19 infusion to Day 282
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.
Time frame
Day 28 (for B-ALL) and Day 90 (for B-NHL) post UCD19 infusionSecondary outcomes
1
Determine the preliminary efficacy of UCD19 CAR-T cells in pediatric patients with B-ALL during the expansion phase
Rate of patients who have morphologic remission post infusion for B-ALL as assessed by bone marrow morphology.
Time frame
Day 602
Determine the preliminary efficacy of UCD19 CAR-T cells in pediatric patients with B-ALL during the expansion phase
Rate of patients with radiographic remission post infusion for B-NHL
Time frame
Day 903
Determine the preliminary efficacy of UCD19 CAR-T cells in pediatric patients with B-ALL during the expansion phase
Rate of efficacy as assessed by bone marrow minimal residual disease assessment by flow cytometric analysis and next generation sequencing for B-ALL patients
Time frame
Months 1, 2, 3, 6, and 124
Determine the preliminary efficacy of UCD19 CAR-T cells in pediatric patients with B-ALL during the expansion phase
Median duration of remission as assessed by bone marrow minimal residual disease assessment by flow cytometric analysis and next generation sequencing for B-ALL patients
Time frame
Months 1, 2, 3, 6, and 12Sponsors and contacts
Click on the lead sponsor to view all of their trials.
University of Colorado, Denver
Lead sponsor
Children's Hospital Colorado
Collaborator
Source ClinicalTrials.gov