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Phase 1 Study of Allo-RevCAR01-T-CD123 in Patients With Selected CD123 Positive Hematologic Malignancies (1b Dose Expansion) (RevSTAR-123)

21. september 2026 oppdatert av: AvenCell Europe GmbH

Multisenter, åpent, fase 1-studie av Allo-RevCAR01-T-CD123 som består av genetisk modifiserte T-celler som bærer omvendte kimære antigenreseptorer (Allo RevCAR01 T) i kombinasjon med CD123-målmodul (R-TM123) for behandling av pasienter med Utvalgte hematologiske maligniteter 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.

Studieoversikt

Status

Rekruttering

Forhold

Intervensjon / Behandling

Studietype

Intervensjonell

Registrering (Antatt)

37

Fase

  • Fase 1

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

Studer Kontakt Backup

Studiesteder

  • Nederland
    • Gelderland
      • Rotterdam, Gelderland, Nederland, 3015
        • Rekruttering
        • Erasmus University Medical Center
        • Ta kontakt med:
    • HV
      • Amsterdam, HV, Nederland, 1081
    • RB Groningen
      • Groningen, RB Groningen, Nederland, 9700
        • Fullført
        • University Medical Center Groningen (UMCG)
  • Tyskland
      • Cologne, Tyskland, 50937
        • Fullført
        • Universitätsklinikum Köln
      • Essen, Tyskland, 45147
      • Frankfurt, Tyskland, 60590
      • Hamburg, Tyskland, 20246
        • Har ikke rekruttert ennå
        • Universitätsklinikum Hamburg-Eppendorf
        • Ta kontakt med:
      • Hanover, Tyskland
      • Heidelberg, Tyskland, 69120
    • Baden-Wurttemberg
      • Ulm, Baden-Wurttemberg, Tyskland, 89081
    • Bavaria
      • Munich, Bavaria, Tyskland, 81377
      • Würzburg, Bavaria, Tyskland, 97080
        • Rekruttering
        • Universitätsklinikum Würzburg
        • Ta kontakt med:
    • Hesse
      • Marburg, Hesse, Tyskland, 35032
    • Saxony
      • Dresden, Saxony, Tyskland, 01307
        • Rekruttering
        • Universitätsklinikum Dresden
        • Ta kontakt med:
    • State of Berlin
      • Berlin, State of Berlin, Tyskland, 13353

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

18 år og eldre (Voksen, Eldre voksen)

Tar imot friske frivillige

Nei

Kjønn som er kvalifisert for studier

Alle

Beskrivelse

Inclusion Criteria (Dose Expansion):

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.

  1. 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.
  2. 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.
  3. 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.

Exclusion Criteria (Dose Expansion):

  1. Acute promyelocytic leukemia (t15;17) or myeloproliferative neoplasm (MPN) per WHO 2022 diagnostic criteria.
  2. AML with only extramedullary manifestations (e.g., chloroma, primary myeloid sarcoma).
  3. Active manifestation of AML in the central nervous system.
  4. Bone marrow failure syndromes.
  5. 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.
  6. Active pulmonary disease with clinically relevant hypoxia (SpO₂ <92% on room air or daily need for supplemental oxygen).
  7. Parkinson's disease or epilepsy with clinical symptoms in the previous 6 months .
  8. Stroke, seizure, or intracranial hemorrhage in the past 12 months.
  9. History or presence of disseminated intravascular coagulation (DIC), deep vein thrombosis or thromboembolism within 3 months prior to start of treatment.
  10. Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
  11. Presence of hemorrhagic cystitis
  12. Other toxicity from prior anticancer treatment has not resolved to Grade ≤1 or baseline.
  13. Allogeneic stem cell transplantation within last 2 months or GvHD requiring systemic immunosuppressive therapy.
  14. Vaccination with live viruses < 2 weeks prior to lymphodepletion therapy.
  15. Major surgery within 28 days prior to start of R-TM123 infusion.
  16. 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.
  17. 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.
  18. Treatment with anti-leukemic therapy within 4 weeks or 5 half-lives (whichever is shorter) prior to lymphodepletion.
  19. Prior treatment with gene modified cell products.
  20. Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants.
  21. Pregnant or breastfeeding women.
  22. 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.
  23. 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).
  24. 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.)
  25. Known hypersensitivity to cellular component (Allo-RevCAR01-T) and/or TM (R-TM123) excipients or to compounds of the lymphodepletion therapy, tocilizumab, or corticosteroids.
  26. Evidence that the participant is not likely or able to follow the study protocol (e.g., lacking compliance) in the judgment of the investigator.
  27. Participant unable to understand the informed consent and possible consequences of the participation in the clinical trial in the judgment of the investigator.

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: N/A
  • Intervensjonsmodell: Enkeltgruppeoppdrag
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Allo-RevCAR01-T-CD123 treatment

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).
Annen: Cyclophosphamide (Non-IMP, Lymphodepletion)

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

Annen: Fludarabine (Non-IMP, Lymphodepletion)

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

Legemiddel: R-TM123

Intravenous infusion over 20 days

Andre navn:
  • R-TM123 er en komponent i Allo-RevCAR01-T-CD123-behandlingen
Legemiddel: Allo-RevCAR01-T

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

Andre navn:
  • Allo-RevCAR01-T er en komponent i Allo-RevCAR01-T-CD123-behandlingen

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Safety and tolerability
Tidsramme: At the end of cycle 1 (in total 28 days, given no treatment interruptions)

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)

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Response rate to consolidation treatment cycles
Tidsramme: At any timepoint until end of study (6 months after the end of last R-TM123 administration)
  • 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
At any timepoint until end of study (6 months after the end of last R-TM123 administration)
Survival rates
Tidsramme: At end of study visit (6 months after the end of last R-TM123 administration)
  • Progression free survival
  • Overall survival
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
Tidsramme: At any timepoint until end of study (6 months after the end of last R-TM123 administration)
  • 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
At any timepoint until end of study (6 months after the end of last R-TM123 administration)

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

AvenCell Europe GmbH

Samarbeidspartnere

Allucent (NL) BV

Etterforskere

  • Studieleder: Manfred Klevesath, MD, AvenCell Therapeutics, Inc.

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Faktiske)

3. januar 2024

Primær fullføring (Antatt)

1. mai 2027

Studiet fullført (Antatt)

1. januar 2028

Datoer for studieregistrering

Først innsendt

23. juni 2023

Først innsendt som oppfylte QC-kriteriene

14. juli 2023

Først lagt ut (Faktiske)

17. juli 2023

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

24. september 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

21. september 2026

Sist bekreftet

1. september 2026

Mer informasjon

Begreper knyttet til denne studien

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • AVC-201-01
  • 2022-501797-19-00 (Annen identifikator: EU CT Number)

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Nei

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

Denne informasjonen ble hentet direkte fra nettstedet clinicaltrials.gov uten noen endringer. Hvis du har noen forespørsler om å endre, fjerne eller oppdatere studiedetaljene dine, vennligst kontakt register@clinicaltrials.gov. Så snart en endring er implementert på clinicaltrials.gov, vil denne også bli oppdatert automatisk på nettstedet vårt. .

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