Phase 1 Study of UniCAR02-T-CD123 in Patients With Selected CD123 Positive Hematologic Malignancies

NCT04230265 | Terminated Phase 1 DMC

• 3 other identifiers: UC02-123-012019-001339-302024-515827-12-00
• Study Type: interventional
• Target: 32
• Locations: 2 countries
• Sites: 10

Brief Summary

This dose-escalating phase I trial assesses for the first time the safety, the side effects and the harmlessness, as well as the therapeutical benefit of the new study drug UniCAR02-T-CD123 in patients with hematologic and lymphatic malignancies positive for CD123 marker. The UniCAR02-T-CD123 drug is a combination of a cellular component (UniCAR02-T) with a recombinant antibody derivative (TM123) which together forms the active drug.

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (3)

• Safety and tolerability

  Incidence and intensity of adverse events graded according to CTCAE V5.0 with the exception of CRS and ICANS graded according to Lee et al. 2014 and Lee et al. 2019 respectively

  Infusion period of TM123 (up to 20 days) + 7 days resp. 14 days in patients with complete blast clearance during the IC or until Safety Follow-up 1 (infusion period of TM123 + 28 days + 3 months)

• Recommended phase 2 dose (RP2D)

  Establishing recommended phase 2 dose (RP2D) and schedule

  Infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)

• Response

  Complete remission (CR, CRh, CRi, CRMRDneg, CRMRDpos) and partial remission (PR) at any time point and duration of responses

  Infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)

Secondary Outcomes (7)

• Establishing recommended phase 2 dose (RP2D)

  DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)

• Complete (CR, CRh, CRi ) and partial remission (PR)

  until fifteen years after last UniCAR02-T administration

• Disease stabilization (DS)

  until fifteen years after last UniCAR02-T administration

• Best response rate

  until fifteen years after last UniCAR02-T administration

• Progression free survival (PFS)

  until fifteen years after last UniCAR02-T administration

Study Arms (2)

UniCAR02-T-CD123 (4 mg/day TM123)

EXPERIMENTAL

Preconditioning (lymphodepletion) with cyclophosphamide and fludarabine, followed by combination treatment of genetically modified T-cells carrying universal chimeric antigen receptors (UniCAR02-T) with 4 mg/day of the recombinant antibody derivative TM123.

Drug: Cyclophosphamide (Non-IMP); Drug: Fludarabine (Non-IMP); Drug: TM123 (IMP); Drug: UniCAR02-T (IMP)

UniCAR02-T-CD123 (8 mg/day TM123)

EXPERIMENTAL

Preconditioning (lymphodepletion) with cyclophosphamide and fludarabine, followed by combination treatment of genetically modified T-cells carrying universal chimeric antigen receptors (UniCAR02-T) with 8 mg/day of the recombinant antibody derivative TM123.

Drug: Cyclophosphamide (Non-IMP); Drug: Fludarabine (Non-IMP); Drug: TM123 (IMP); Drug: UniCAR02-T (IMP)

Interventions

Cyclophosphamide (Non-IMP) DRUG

Intravenous infusion over 3 days

UniCAR02-T-CD123 (4 mg/day TM123); UniCAR02-T-CD123 (8 mg/day TM123)

Fludarabine (Non-IMP) DRUG

Intravenous infusion over 3 days

UniCAR02-T-CD123 (4 mg/day TM123); UniCAR02-T-CD123 (8 mg/day TM123)

TM123 (IMP) DRUG

Intravenous Infusion for 20 days

UniCAR02-T-CD123 (4 mg/day TM123); UniCAR02-T-CD123 (8 mg/day TM123)

UniCAR02-T (IMP) DRUG

Intravenous infusion of single dose

UniCAR02-T-CD123 (4 mg/day TM123); UniCAR02-T-CD123 (8 mg/day TM123)

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 patients, age ≥ 18 years
• Documented definitive diagnosis of Relapsed or refractory AML (according to standard of care testing) and CD123 positivity of ≥20 % of blasts. MRD+ AML without morphological relapse or refractoriness may be included with the sponsor's approval
• Eastern Cooperative Oncology Group (ECOG) of 0 to 1
• Life expectancy of at least 2 months
• Adequate renal and hepatic laboratory assessments
• Adequate cardiac function
• Long-term venous access existing (e.g. port-system) resp. acceptance of implantation of a device
• Able to give written informed consent
• Weight ≥ 45 kg
• Negative pregnancy test; routinely using a highly effective method of birth control

You may not qualify if:

• Acute promyelocytic leukemia
• AML with only extramedullary manifestations (e.g., chloroma, primary myeloid sarcoma).
• Refractory disease under anti-leukemic treatment lasting longer than 6 months
• Current manifestation of AML in central nervous system
• Bone marrow failure syndromes (e.g. Fanconi anemia, Kostman syndrome, Shwachman syndrome)
• Significant cardiac disease: i.e., heart failure (NYHA III or IV); unstable coronary artery disease, myocardial infarction or serious cardiac ventricular arrhythmias requiring anti-arrhythmic therapy within the last 12 months prior to study entry that may in the Investigator's opinion interfere with participation in the trial.
• Patients undergoing renal dialysis
• Pulmonary disease with clinically relevant hypoxia
• Parkinson's disease, epilepsy, stroke, seizures, significant paresis or aphasia with clinical symptoms in the previous 12 months that may in the Investigator's opinion interfere with participation in the trial.
• Disseminated intravascular coagulation (DIC) within 3 months prior to the planned start of the study treatment.
• Hemorrhagic cystitis
• Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
• Allogeneic stem cell transplantation within last two months or GvHD requiring systemic immunosuppressive therapy
• Vaccination with live viruses within 2 weeks prior to lymphodepletion therapy
• Major surgery within 28 days (prior to start of TM123 infusion)

Sponsors & Collaborators

• AvenCell Europe GmbH: lead
• PHARMALOG Institut für klinische Forschung GmbH: collaborator

Study Sites (10)

Universitätsklinikum Ulm

Ulm, Baden-Wurttemberg, 89081, Germany

Location

Klinikum der Universität München

Munich, Bavaria, 81377, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Bavaria, 97080, Germany

Location

Philipps-Universität Marburg

Marburg, Hesse, 35032, Germany

Location

Uniklinik RWTH Aachen

Aachen, North Rhine-Westphalia, 52074, Germany

Location

Universitätsklinikum Dresden

Dresden, Saxony, 01307, Germany

Location

Universitätsklinikum Leipzig

Leipzig, Saxony, 04103, Germany

Location

Universitätsklinikum Hamburg-Eppendorf

Hamburg, 20246, Germany

Location

Erasmus University Medical Center

Rotterdam, Gelderland, 3015, Netherlands

Location

Universitair Medisch Centrum Groningen

Groningen, GZ, 9713, Netherlands

Location

Related Publications (1)

• Loff S, Dietrich J, Meyer JE, Riewaldt J, Spehr J, von Bonin M, Grunder C, Swayampakula M, Franke K, Feldmann A, Bachmann M, Ehninger G, Ehninger A, Cartellieri M. Rapidly Switchable Universal CAR-T Cells for Treatment of CD123-Positive Leukemia. Mol Ther Oncolytics. 2020 Apr 29;17:408-420. doi: 10.1016/j.omto.2020.04.009. eCollection 2020 Jun 26.

  PMID: 32462078 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Cyclophosphamide; fludarabine; Inosine Monophosphate

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; Inosine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: In the expansion cohort 2 different TM123 dose levels shall be compared descriptively.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase 1b Dose Expansion: An expansion cohort of up to 20 patients was initiated.

Study Record Dates

• First Submitted: January 10, 2020
• First Posted: January 18, 2020
• Study Start: January 28, 2020
• Primary Completion: April 11, 2025
• Study Completion: April 11, 2025
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

DE (8); NL (2)