Phase 1 Study of Allo-RevCAR01-T-CD123 in Patients With Selected CD123 Positive Hematologic Malignancies

NCT05949125 | Recruiting Phase 1 DMC

• 2 other identifiers: AVC-201-012022-501797-19-00
• Study Type: interventional
• Target: 80
• Locations: 2 countries
• Sites: 11

Brief Summary

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.

Conditions

Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia Refractory

Outcome Measures

Primary Outcomes (3)

• 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)

Secondary Outcomes (4)

• Response rate to consolidation treatment cycles

  At any timepoint until end of study (6 months after the end of last R-TM123 administration)

• Establishing recommended Phase 2 dose (RP2D)

  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)

Study Arms (1)

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.

Other: Cyclophosphamide (Non-IMP, Lymphodepletion); Other: Fludarabine (Non-IMP, Lymphodepletion); Drug: R-TM123; Drug: Allo-RevCAR01-T

Interventions

Cyclophosphamide (Non-IMP, Lymphodepletion) OTHER

Intravenous infusion over 3 days (d-5 to d-3)

Allo-RevCAR01-T-CD123 treatment

Fludarabine (Non-IMP, Lymphodepletion) OTHER

Intravenous infusion over 3 days (d-5 to d-3)

Allo-RevCAR01-T-CD123 treatment

R-TM123 DRUG

Intravenous infusion over 20 days

Also known as: R-TM123 is one component of the Allo-RevCAR01-T-CD123 treatment

Allo-RevCAR01-T-CD123 treatment

Allo-RevCAR01-T DRUG

Allo-RevCAR01-T will be administered as IV infusion on Treatment day 1.

Also known as: Allo-RevCAR01-T is one component of the Allo-RevCAR01-T-CD123 treatment

Allo-RevCAR01-T-CD123 treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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)
• 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,
• without hyperproliferative disease requiring cytoreductive treatment,
• exceptions to BM blast criterion are only possible in minor deviations in timing and/or blast count in clinically stable patients, and only with written sponsor approval. Exceptions to minimum CD123 expression are not allowed.
• 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:
• MRD positivity must be based on assays and markers supported by consensus guidelines \[Heuser2021\] and in the judgment of the investigator must confer negative prognostic risk highly likely to result in relapse.
• must have received or be ineligible for allogeneic stem cell transplant.
• \. Able to give written informed consent. 10. Weight ≥45 kg. 11. Negative pregnancy; routinely using a highly effective method of birth control

You may not qualify if:

• 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
• Cardiac disease: heart failure (New York Heart Association III or IV); unstable coronary artery disease, myocardial infarction, or serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within the last 6 months prior to study entry.
• Active pulmonary disease with clinically relevant hypoxia
• Parkinson's disease or epilepsy with clinical symptoms in the previous 12 months .
• Stroke, seizure, or intracranial hemorrhage in the past 12 months.
• History or presence of disseminated intravascular coagulation (DIC), deep vein thrombosis or thromboembolism within 3 months prior to start of treatment.
• Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
• Presence of hemorrhagic cystitis
• Other toxicity from prior anticancer treatment has not resolved to Grade ≤1 or baseline.
• Allogeneic stem cell transplantation within last 2 months or GvHD requiring systemic immunosuppressive therapy.
• Vaccination with live viruses \< 2 weeks prior to lymphodepletion therapy.
• Major surgery within 28 days prior to start of R-TM123 infusion.

Sponsors & Collaborators

• AvenCell Europe GmbH: lead
• Allucent (NL) BV: collaborator

Study Sites (11)

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

RECRUITING

Klinikum der Universität München

Munich, Bavaria, 81377, Germany

RECRUITING

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

RECRUITING

Universitätsklinikum Marburg

Marburg, Hesse, 35032, Germany

RECRUITING

Universitätsklinikum Dresden

Dresden, Saxony, 01307, Germany

RECRUITING

Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

RECRUITING

Universitätsklinikum Köln

Cologne, 50937, Germany

RECRUITING

Medizinische Hochschule Hannover

Hanover, Germany

RECRUITING

Erasmus University Medical Center

Rotterdam, Gelderland, 3015, Netherlands

RECRUITING

Amsterdam University Medical Center

Amsterdam, HV, 1081, Netherlands

NOT YET RECRUITING

University Medical Center Groningen (UMCG)

Groningen, RB Groningen, 9700, Netherlands

NOT YET RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Tapan Maniar, MD

  AvenCell Europe GmbH

  STUDY DIRECTOR

Central Study Contacts

Katja Jersemann, Dr.

CONTACT

0493514466450; AVC-201-01@avencell.com

Martina Raupach

CONTACT

0493514466450; AVC-201-01@avencell.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 23, 2023
• First Posted: July 17, 2023
• Study Start: January 3, 2024
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: May 14, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8); NL (3)