Acute Myeloid Leukemia, in RelapsePhase 1RevSTAR-123NCT05949125
Phase 1 Study of Allo-RevCAR01-T-CD123 in Patients With Selected CD123 Positive Hematologic Malignancies (1b Dose Expansion)
A Phase 1 study testing Cyclophosphamide (Non-IMP, Lymphodepletion), Fludarabine (Non-IMP, Lymphodepletion) and R-TM123 in people with Acute Myeloid Leukemia, in Relapse and Acute Myeloid Leukemia Refractory, run by AvenCell Europe GmbH at 15 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia Refractory
- What is being tested?
- Cyclophosphamide (Non-IMP, Lymphodepletion), Fludarabine (Non-IMP, Lymphodepletion) and R-TM123
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 15 sitesin 2 countries
- Study dates
- 3 Jan 2024to Jan 2028
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. 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.
- 9. 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.
- 11. Negative pregnancy; routinely using a highly effective method of birth control.
Who cannot join
- 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).
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- 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.
- Prior malignancy in the past 3 years or any malignancy requiring ongoing active therapy other than adjuvant endocrine therapy. Participants with malignancy within the last 3 years, but with resected or ablated tumors, such as basal cell carcinoma of skin, carcinoma-in-situ of the cervix, or other tumors considered cured may be considered for the study with Sponsor approval.
- Treatment with any investigational drug substance or experimental therapy within 4 weeks or 5 half-lives (whichever is shorter) of the substance prior to lymphodepletion.
- Treatment with anti-leukemic therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to lymphodepletion.
- Prior treatment with gene modified cell products.
- Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants.
- Pregnant or breastfeeding women.
- Psychologic disorders with treatment modifications required within the last 3 months, drug and/or significant active alcohol abuse as per investigator's medical judgement. Depression or anxiety due to presence of the underlying malignancy may be exempted with Sponsor approval.
- History of human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV).
- Known presence of autoantibodies against lupus La protein (La)/ Sjögren syndrome type B antigen (SS-B) or presence or history of autoimmune diseases associated with such antibodies. (Results from recent sampling are not required for eligibility unless MH or other facts indicate La/SS-B would likely be positive.)
- Known hypersensitivity to cellular component (Allo-RevCAR01-T) and/or TM (R-TM123) excipients or to compounds of the lymphodepletion therapy, tocilizumab, or corticosteroids.
- Evidence that the participant is not likely or able to follow the study protocol (e.g., lacking compliance) in the judgment of the investigator.
- Participant unable to understand the informed consent and possible consequences of the participation in the clinical trial in the judgment of the investigator.
Trial locations and contacts
15 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
15 sites in 2 countries
Germany12 sites, 11 recruiting
- Recruiting
Charité Universitätsmedizin Berlin
Berlin, State of Berlin, 13353
Jörg Westermann, Prof., joerg.westermann@charite.de
- Completed
Universitätsklinikum Köln
Cologne, 50937
- Recruiting
Universitätsklinikum Dresden
Dresden, Saxony, 01307
Martin Wermke, Prof., martin.wermke@ukdd.de
- Not yet recruiting
Universitätsklinikum Essen
Essen, 45147
Bastian von Tresckow, Prof., bastian.vontresckow@uk-essen.de
- Not yet recruiting
Universitätsklinikum Frankfurt
Frankfurt, 60590
Gesine Bug, MD, gesine.bug@unimedizin-ffm.de
- Not yet recruiting
Universitätsklinikum Hamburg-Eppendorf
Hamburg, 20246
Franziska Westendorf, MD, f.westendorf@uke.de
- Recruiting
Medizinische Hochschule Hannover
Hanover
Felizitas Thol, Prof., Thol.Felicitas@mh-hannover.de
- Not yet recruiting
Universitätsklinikum Heidelberg
Heidelberg, 69120
Tim Sauer, MD, tim.sauer@med.uni-heidelberg.de
- Recruiting
Universitätsklinikum Marburg
Marburg, Hesse, 35032
Stephan Metzelder, Prof., metzelde@med.uni-marburg.de
- Recruiting
Klinikum der Universität München
Munich, Bavaria, 81377
Marion Subklewe, Prof., Marion.Subklewe@med.uni-muenchen.de
- Recruiting
Universitätsklinikum Ulm
Ulm, Baden-Wurttemberg, 89081
Elisa Sala, MD, elisa.sala@uniklinik-ulm.de
- Recruiting
Universitätsklinikum Würzburg
Würzburg, Bavaria, 97080
Chatterjee Manik, MD, Chatterjee_m@ukw.de
Netherlands3 sites, 2 recruiting
- Recruiting
Amsterdam University Medical Center
Amsterdam, HV, 1081
Arjan van de Loosdrecht, Prof., a.vandeloosdrecht@amsterdamumc.nl
- Completed
University Medical Center Groningen (UMCG)
Groningen, RB Groningen, 9700
- Recruiting
Erasmus University Medical Center
Rotterdam, Gelderland, 3015
Mojca Jongen-Lavrencic, Dr., m.lavrencic@erasmusmc.nl
About this study
Official title: Multicenter, Open-label, Phase 1 Study of Allo-RevCAR01-T-CD123 Consisting of Genetically Modified T Cells Carrying Reverse Chimeric Antigen Receptors (Allo RevCAR01 T) in Combination With CD123 Target Module (R-TM123) for the Treatment of Patients With Selected Hematologic Malignancies Positive for CD123
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.
- Being tested
- Cyclophosphamide (Non-IMP, Lymphodepletion), Fludarabine (Non-IMP, Lymphodepletion), R-TM123, Allo-RevCAR01-T
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cyclophosphamide (Non-IMP, Lymphodepletion)Other
Intravenous infusion over 3 days (d-5 to d-3)
Fludarabine (Non-IMP, Lymphodepletion)Other
Intravenous infusion over 3 days (d-5 to d-3)
R-TM123Drug
Also called R-TM123 is one component of the Allo-RevCAR01-T-CD123 treatment
Intravenous infusion over 20 days
Allo-RevCAR01-TDrug
Also called Allo-RevCAR01-T is one component of the Allo-RevCAR01-T-CD123 treatment
Allo-RevCAR01-T will be administered as IV infusion on Treatment Day 1
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Other: Cyclophosphamide (Non-IMP, Lymphodepletion); Other: Fludarabine (Non-IMP, Lymphodepletion); Drug: R-TM123; Drug: Allo-RevCAR01-T |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: At the end of cycle 1 (in total 28 days, given no treatment interruptions)
Secondary outcomes (3)
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
Measured: At any timepoint until end of study (6 months after the end of last R-TM123 administration)
Survival rates
- Progression free survival
- Overall survival
Measured: 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
- 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
Measured: At any timepoint until end of study (6 months after the end of last R-TM123 administration)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2023
- Study start3 Jan 2024
- Primary completionMay 2027 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Myeloid Leukemia, in RelapseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AvenCell Europe GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Allucent (NL) BV
- Responsible party
- Sponsor
- Investigators
- Manfred Klevesath, MD, Study director, AvenCell Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05949125
- Sponsor's protocol ID
- AVC-201-01
- Other IDs
- 2022-501797-19-00
- Acronym
- RevSTAR-123
- Status last verified
- Sep 2026
- First submitted
- 23 Jun 2023
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No