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Dose-escalating Trial With Allo-RevCAR01-T Cells in Combination With CD123 Target Module (R-TM123) for Participants With Selected Hematologic Malignancies Positive for CD123

Recruiting
18 years of age
Both
Phase 1

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Overview

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.

Eligibility

Inclusion Criteria:

  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 (defined as ≥20% of leukemic cells expressing CD123 at any point in the course of disease)
    • Participants with MRD+ AML are eligible but must meet specific criteria i. 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.
             ii. Must have received or be ineligible for allogeneic stem cell transplant. iii. Must
             be approved by the Sponsor for inclusion in the study.
          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. Permanent venous access existing (e.g., port-system) or willing to have such a device
             inserted.
          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:
          1. Acute promyelocytic leukemia (t15;17).
          2. AML with only extramedullary manifestations (e.g., chloroma, primary myeloid sarcoma)
          3. Acute manifestationof 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
          7. Parkinson's disease or epilepsy with clinical symptoms in the previous 12 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. Toxicity from prior anticancer treatment has not resolved to Grade ≤1 or baseline.
         12. Allogeneic stem cell transplantation within last 2 months or GvHD requiring
             immunosuppressive therapy.
         13. Vaccination with live viruses <2 weeks prior to lymphodepletion therapy.
         14. Major surgery within 28 days prior to start of R-TM123 infusion.
         15. Prior malignancy in the past 3 years or any malignancy requiring ongoing active
             therapy other than adjuvant endocrine therapy. Participants with resected or ablated
             tumors, such as basal cell carcinoma of skin, carcinoma-in-situ of the cervix, or
             other tumors considered cured by local treatment may be considered for the study with
             Sponsor approval.
         16. 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.
         17. Treatment with anti-leukemic therapy within 4 weeks or 5 half-lives (whichever is
             shorter) prior to lymphodepletion.
         18. Prior treatment with gene modified cell products.
         19. Use of checkpoint inhibitors within 5 half-lives of the specific drug.
         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. 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
         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 judgement of the investigator.

Study details

Acute Myeloid Leukemia, in Relapse, Acute Myeloid Leukemia Refractory

NCT05949125

AvenCell Europe GmbH

14 May 2024

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