Phase 1 Study of Allo-RevCAR01-T-CD123 in Patients With Selected CD123 Positive Hematologic Malignancies
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAvenCell Europe GmbH
About this trial
The Allo-RevCAR01-T-CD123 drug is a combination of a cellular component (Allo-RevCAR01-T) with a recombinant antibody derivative (R-TM123), which together form the active drug. The cellular component Allo-RevCAR01-T consists of an allogeneic human T-cell genetically multi-edited and expressing a reversed, universal chimeric antigen receptor (RevCAR) presenting an extracellular peptide epitope (RevCAR epitope). R-TM123 functions as a bridging module between Allo-RevCAR01-T and a CD123-expressing target cancer cell by selectively binding the RevCAR epitope and CD123.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
For Phase 1a escalation part of the trial Participants with CD123+ AML (defined as ≥20% of leukemic cells expressing CD123 at any point in the course of disease)
For Phase 1b expansion part of the trial (Phase 1b) Participants with CD123+ AML (defined as ≥20% of leukemic cells expressing CD123 at any point in the course of disease)
up to 3rd relapse for whom all standard or life-extending therapies have failed and for whom no potentially curative therapies are available or who are intolerant to such therapies
having up to 30% blasts in a bone marrow assessment at either screening or prescreening, or having between 30% and 40% blasts for two consecutive bone marrow assessments with a minimum of one month and no more than two months apart,
Disqualifiers
Acute promyelocytic leukemia (t15;17).
AML with only extramedullary manifestations (e.g., chloroma, primary myeloid sarcoma)
Acute manifestationof AML in the central nervous system.
Bone marrow failure syndromes
Trial design
Design model
Parallel
Treatments tested in this trial
Cyclophosphamide (Non-IMP, Lymphodepletion)
Other interventionIntravenous infusion over 3 days (d-5 to d-3)
Fludarabine (Non-IMP, Lymphodepletion)
Other interventionIntravenous infusion over 3 days (d-5 to d-3)
R-TM123
DrugIntravenous infusion over 20 days
Allo-RevCAR01-T
DrugAllo-RevCAR01-T will be administered as IV infusion on Treatment day 1.
Treatment groups
80 Participants
are divided into 1 treatment groupGroup A: Allo-RevCAR01-T-CD123 treatmentExperimental treatment 4 interventions
Trial outcomes
Primary outcomes
1
To assess the safety profile of the treatment
Incidence and intensity of adverse events (AEs) graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, except for cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), tumor lysis syndrome, and graft versus host disease (GvHD), which will be graded according to widely accepted specialized criteria
Time frame
At the end of cycle 1 (in total 28 days, given no treatment interruptions)2
To determine the incidence of dose-limiting toxicities (DLT)
Incidence of DLTs
Time frame
At the end of cycle 1 (in total 28 days, given no treatment interruptions)3
To determine the maximum tolerated dose (MTD)
MTD
Time frame
At the End of Cycle 1 (in total 28 days, given no treatment interruptions)Secondary outcomes
1
Response rate to consolidation treatment cycles
* Complete remission (CR, CRc, CRh, CRi, CRMRDneg, CRMRDpos) * Morphologic leukemia free state (MLFS), * Partial remission (PR) * Overall response rate (ORR) * Best response rate * Duration of response
Time frame
At any timepoint until end of study (6 months after the end of last R-TM123 administration)2
Establishing recommended Phase 2 dose (RP2D)
Based on assessments of MTD and DLTs
Time frame
At any timepoint until end of study (6 months after the end of last R-TM123 administration)3
Survival rates
* Progression free survival * Overall survival
Time frame
At end of study visit (6 months after the end of last R-TM123 administration)4
Evidence of biological and clinical activity including best response rate
* Complete remission (CR, CRh, CRi, CRMRDneg, CRMRDpos) * Morphologic leukemia free state (MLFS) * Partial remission (PR) * Overall response rate (ORR) * Best response rate * Duration of response * PFS * OS
Time frame
At any timepoint until end of study (6 months after the end of last R-TM123 administration)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
AvenCell Europe GmbH
Lead sponsor
Allucent (NL) BV
Collaborator
Source ClinicalTrials.gov