Phase 1 Study of Allo-RevCAR01-T-CD123 in Patients With Selected CD123 Positive Hematologic Malignancies (1b Dose Expansion)

NCT05949125 | Recruiting Phase 1 DMC

• 2 other identifiers: AVC-201-012022-501797-19-00
• Study Type: interventional
• Target: 37
• Locations: 2 countries
• Sites: 15

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 (1)

• Safety and tolerability

  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)

Secondary Outcomes (3)

• Response rate to consolidation treatment cycles

  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 (from Day -5 to Day -3), 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. All participants who tolerate Cycle 1 of R-TM123 and Allo-RevCAR01-T without clear disease progression or safety or other contraindications after Cycle 1, will be considered for consolidation cycles of up to 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 overall treatment time (whichever occurs first).

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

Interventions

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

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

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. Participants with CD123+ AML with morphologically relapsed or refractory disease (\>5% BM blasts). CD123 positivity is defined as ≥20% of leukemic cells expressing CD123 at any point in the course of disease.
• Up to third 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.
• Without prior myeloproliferative neoplasm (MPN) or MDS/MPN (including leukemic transformation of MPN, "blast phase", and "accelerated phase" MPN), and without hyperproliferative disease requiring cytoreductive treatment within 4 weeks from the screening or with WBC above ULN at screening.
• Exceptions to minimum CD123 expression are not allowed. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. 5. Life expectancy of at least 3 months in the judgment of the investigator. 6. Adequate renal and hepatic laboratory assessments. 7. Adequate cardiac function. 8. Long-term central venous access existing (e.g., tunneled CV catheter or port-system) or willing to have such a device inserted to ensure continuous R-TM123 administration.
• \. Able to give written informed consent. 10. Weight is greater than the minimum weight required for a specific batch to ensure that the dose administered does not exceed 10\^5 TCR+ cells/kg of patient weight.
• \. Negative pregnancy; routinely using a highly effective method of birth control.

You may not qualify if:

• Acute promyelocytic leukemia (t15;17) or myeloproliferative neoplasm (MPN) per WHO 2022 diagnostic criteria.
• AML with only extramedullary manifestations (e.g., chloroma, primary myeloid sarcoma).
• Active manifestation of 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 (SpO₂ \<92% on room air or daily need for supplemental oxygen).
• Parkinson's disease or epilepsy with clinical symptoms in the previous 6 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 (15)

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, State of Berlin, 13353, Germany

RECRUITING

Universitätsklinikum Köln

Cologne, 50937, Germany

COMPLETED

Universitätsklinikum Essen

Essen, 45147, Germany

NOT YET RECRUITING

Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

NOT YET RECRUITING

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

NOT YET RECRUITING

Medizinische Hochschule Hannover

Hanover, Germany

RECRUITING

Universitätsklinikum Heidelberg

Heidelberg, 69120, Germany

NOT YET RECRUITING

Erasmus University Medical Center

Rotterdam, Gelderland, 3015, Netherlands

RECRUITING

Amsterdam University Medical Center

Amsterdam, HV, 1081, Netherlands

RECRUITING

University Medical Center Groningen (UMCG)

Groningen, RB Groningen, 9700, Netherlands

COMPLETED

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

• Manfred Klevesath, MD

  AvenCell Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Katja Jersemann, Dr.

CONTACT

0493514466450; AVC-201-01@avencell.com

Antje Warth, Dr.

CONTACT

0493514466450; AVC-201-01@avencell.com

Study Design

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

Model Details: This is a Phase 1, open-label, multicenter, first-in-human study initially using a Bayesian optimal interval for combinations (BOIN comb) dose escalation design, that was extended by a 3+3 dose escalation phase. Once dose escalation Phase 1a is completed, a non-randomized Phase 1b expansion phase of up to 20 participants with a single dose (RP2D) will be started seamlessly at the dose level with the most favorable benefit-risk ratio observed in Phase 1a.

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: September 24, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (12); NL (3)