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

Acute Myeloid Leukemia, in Relapse Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05949125
• Other study ID #: AVC-201-01
• Secondary ID: 2022-501797-19-0
• Status: Recruiting
• Phase: Phase 1
• Start date: January 3, 2024
• Est. completion date: June 2026

Study information

• Verified date: April 2024
• Source: AvenCell Europe GmbH
• Contact: Katja Jersemann, Dr.
• Phone: +493514466450
• Email: AVC-201-01[@]avencell.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 37
• Est. completion date: June 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia Refractory
• Acute Myeloid Leukemia, in Relapse
• Hematologic Neoplasms
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Other:
• Cyclophosphamide (Non-IMP, Lymphodepletion)
Intravenous infusion over 3 days (d-5 to d-3)
• Fludarabine (Non-IMP, Lymphodepletion)
Intravenous infusion over 3 days (d-5 to d-3)

Drug:
• R-TM123
Intravenous infusion over 20 days
• Allo-RevCAR01-T
A single dose of Allo-RevCAR01-T will be administered as IV infusion on Treatment day 1. Allo-RevCAR01-T will not be administered again within this study.

Locations

Country	Name	City	State
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Universitätsklinikum Dresden	Dresden	Sachsen
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Köln	Köln
Germany	Universitätsklinikum Marburg	Marburg	Hessen
Germany	Klinikum der Universität München	Munich	Bavaria
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg
Germany	Universitätsklinikum Würzburg	Würzburg	Bayern
Netherlands	Amsterdam University Medical Center	Amsterdam	HV
Netherlands	University Medical Center Groningen (UMCG)	Groningen	RB Groningen
Netherlands	Erasmus University Medical Center	Rotterdam	GD

Sponsors (2)

Lead Sponsor	Collaborator
AvenCell Europe GmbH	Allucent (NL) BV

Countries where clinical trial is conducted

Germany,  Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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)
Primary	To determine the maximum tolerated dose (MTD)	MTD	At the End of Cycle 1 (in total 28 days, given no treatment interruptions)
Secondary	Evidence of biological and clinical activity including best response rate	Complete remission (CR, CRh, CRi, CRMRDneg, CRMRDpos); Partial remission (PR); Overall response rate (ORR); Stable disease (SD); Best response rate; Duration of response	At any timepoint until end of study (6 months after the end of last R-TM123 administration)
Secondary	Survival rates	Progression free survival; Overall survival	At end of study visit (6 months after the end of last R-TM123 administration)
Secondary	Response rate to consolidation treatment cycls	Complete remission (CR, CRc, CRh, CRi, CRMRDneg, CRMRDpos); Morphologic leukemia free state (MLFS),; Partial remission (PR); Overall response rate (ORR); Stable disease (SD); Best response rate; Duration of response	At any timepoint until end of study (6 months after the end of last R-TM123 administration)
Secondary	Establishing recommended Phase 2 dose (RP2D)	Based on assessments of MTD and DLTs	At any timepoint until end of study (6 months after the end of last R-TM123 administration)