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| ID | Type | Description | Link |
|---|---|---|---|
| 2022-501797-19-00 | Other Identifier | EU CT Number |
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| Name | Class |
|---|---|
| Allucent (NL) BV | UNKNOWN |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Allo-RevCAR01-T-CD123 treatment | Experimental | Following lymphodepleting therapy, R-TM123 will be administered as continuous infusion from Cycle 1 Day 1 and then will continue for 20 days. Allo-RevCAR01-T will be administered on Day 1. Participants who tolerate Cycle 1 of R-TM123 and Allo-RevCAR01-T without DLT and are not diagnosed with disease progression after Cycle 1, will be considered for consolidation cycles of 12 consecutive days each of continuous IV infusion of R-TM123 until relapse, unacceptable toxicity, potentially curative treatment option (alloHSCT), consent withdrawal, or maximum one year treatment time. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cyclophosphamide (Non-IMP, Lymphodepletion) | Other | Intravenous infusion over 3 days (d-5 to d-3) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 | At the end of cycle 1 (in total 28 days, given no treatment interruptions) |
| To determine the incidence of dose-limiting toxicities (DLT) | Incidence of DLTs | At the end of cycle 1 (in total 28 days, given no treatment interruptions) |
| To determine the maximum tolerated dose (MTD) | MTD | At the End of Cycle 1 (in total 28 days, given no treatment interruptions) |
| Measure | Description | Time Frame |
|---|---|---|
| Response rate to consolidation treatment cycles |
| At any timepoint until end of study (6 months after the end of last R-TM123 administration) |
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Inclusion Criteria:
1. Male or female participants, age ≥18 years. 2. HLA type of participant must match at HLA B and C loci 3.
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)
(1) 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.
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)
For Phase 1a escalation and Phase 1b expansion part of the trial
Participants with MRD+ AML are potentially eligible but must meet the following criteria:
9. Able to give written informed consent. 10. Weight ≥45 kg. 11. Negative pregnancy; routinely using a highly effective method of birth control
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Katja Jersemann, Dr. | Contact | 0493514466450 | 0 | AVC-201-01@avencell.com |
| Martina Raupach | Contact | 0493514466450 | 0 | AVC-201-01@avencell.com |
| Name | Affiliation | Role |
|---|---|---|
| Tapan Maniar, MD | AvenCell Europe GmbH | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Universitätsklinikum Ulm | Recruiting | Ulm | Baden-Wurttemberg | 89081 | Germany |
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The initial dose escalation (Escalation 1) follows a BOIN comb design with 3 dose levels of Allo-RevCAR01-T and 3 dose levels of R-TM123 resulting in a maximum of 9 dose levels. Given 1 participant dose level cohorts, there will be an inherent stagger between each participant equivalent to the DLT window of 28 days. Dose escalation 1 is followed by a second escalation phase (Escalation 2), including three more R-TM123 dose levels, in combination with the maximum cell dose obtained during the escalation 1. The three additional dose levels will be investigated via a classical 3+3 design (three patients will be treated per dose cohort). If a DLT is observed, three more patients will be added to that dose level.
After escalation, two randomized expansion cohorts (≥10 R/R AML patients each) will compare dose levels to define Phase 2 dosing. If one dose in escalation phase proves clearly superior, a non-randomized Phase 1b expansion with up to 20 patients at that dose may be initiated.
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| Fludarabine (Non-IMP, Lymphodepletion) | Other | Intravenous infusion over 3 days (d-5 to d-3) |
|
| R-TM123 | Drug | Intravenous infusion over 20 days |
|
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| Allo-RevCAR01-T | Drug | Allo-RevCAR01-T will be administered as IV infusion on Treatment day 1. |
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| Establishing recommended Phase 2 dose (RP2D) | Based on assessments of MTD and DLTs | At any timepoint until end of study (6 months after the end of last R-TM123 administration) |
| Survival rates |
| At end of study visit (6 months after the end of last R-TM123 administration) |
| Evidence of biological and clinical activity including best response rate |
| At any timepoint until end of study (6 months after the end of last R-TM123 administration) |
| Klinikum der Universität München | Recruiting | Munich | Bavaria | 81377 | Germany |
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| Universitätsklinikum Würzburg | Recruiting | Würzburg | Bavaria | 97080 | Germany |
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| Universitätsklinikum Marburg | Recruiting | Marburg | Hesse | 35032 | Germany |
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| Universitätsklinikum Dresden | Recruiting | Dresden | Saxony | 01307 | Germany |
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| Charité Universitätsmedizin Berlin | Recruiting | Berlin | 13353 | Germany |
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| Universitätsklinikum Köln | Recruiting | Cologne | 50937 | Germany |
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| Medizinische Hochschule Hannover | Recruiting | Hanover | Germany |
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| Erasmus University Medical Center | Recruiting | Rotterdam | Gelderland | 3015 | Netherlands |
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| Amsterdam University Medical Center | Not yet recruiting | Amsterdam | HV | 1081 | Netherlands |
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| University Medical Center Groningen (UMCG) | Not yet recruiting | Groningen | RB Groningen | 9700 | Netherlands |
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| ID | Term |
|---|---|
| D015470 | Leukemia, Myeloid, Acute |
| ID | Term |
|---|---|
| D007951 | Leukemia, Myeloid |
| D007938 | Leukemia |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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| ID | Term |
|---|---|
| D003520 | Cyclophosphamide |
| C024352 | fludarabine |
| ID | Term |
|---|---|
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
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