Dose-escalating Trial With UniCAR02-T Cells and CD123 Target Module (TM123) in Patients With Hematologic and Lymphatic Malignancies

August 16, 2023 updated by: AvenCell Europe GmbH

Multicenter, Open-label, Adaptive Design Phase I Trial With Genetically Modified T-cells Carrying Universal Chimeric Antigen Receptors (UniCAR02-T) in Combination With CD123 Target Module (TM123) for the Treatment of Patients With Hematologic and Lymphatic Malignancies Positive for CD123

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.

Study Overview

Study Type

Interventional

Enrollment (Estimated)

90

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

      • Hamburg, Germany, 20246
        • Recruiting
        • Universitätsklinikum Hamburg-Eppendorf
        • Contact:
    • Baden-Württemberg
      • Ulm, Baden-Württemberg, Germany, 89081
    • Bavaria
    • Bayern
      • Würzburg, Bayern, Germany, 97080
        • Recruiting
        • Universitätsklinikum Würzburg
        • Contact:
    • Hessen
      • Marburg, Hessen, Germany, 35032
    • NRW
      • Aachen, NRW, Germany, 52074
        • Recruiting
        • UniKlinik RWTH Aachen
        • Contact:
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Recruiting
        • Universitätsklinikum Dresden
        • Contact:
        • Principal Investigator:
          • Martin Wermke, MD
      • Leipzig, Sachsen, Germany, 04103

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Male or female patients, age ≥ 18 years
  2. Documented definitive diagnosis of AML or BPDCN (according to standard of care testing) and CD123 positivity of ≥20 % of blasts. In the case of MRD+ AML, if there are insufficient blasts at screening for CD123 testing, the most recent available sample with sufficient blasts should be used.

    - Relapsed or refractory AML/BPDCN

  3. Eastern Cooperative Oncology Group (ECOG) of 0 to 1
  4. Life expectancy of at least 2 months
  5. Adequate renal and hepatic laboratory assessments
  6. Adequate cardiac function
  7. Permanent venous access existing (e.g. port-system) resp. acceptance of implantation of a device
  8. Able to give written informed consent
  9. Weight ≥ 45 kg
  10. Negative pregnancy; routinely using a highly effective method of birth control

Exclusion Criteria:

  1. Acute promyelocytic leukemia (t15;17)
  2. Refractory disease under anti-leukemic treatment lasting longer than 6 months
  3. Manifestation of AML or BPDCN in central nervous system
  4. Bone marrow failure syndromes
  5. 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 6 months prior to study entry
  6. Patients undergoing renal dialysis
  7. Pulmonary disease with clinical relevant hypoxia
  8. Parkinson, epilepsy and, stroke or presence or history of seizures, paresis, aphasia or intracranial hemorrhage
  9. Presence of disseminated intravascular coagulation (DIC) or thromboembolism, or history of such within 3 months prior to start of treatment
  10. Hemolytic anemia
  11. Multiple sclerosis
  12. Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
  13. Presence of urotoxicity from previous chemo- or radiotherapy or urinary outflow obstruction
  14. Allogeneic stem cell transplantation within last two months or Graft versus host disease (GvHD) requiring immunosuppressive therapy
  15. Vaccination with live viruses less than 2 weeks prior lymphodepletion therapy
  16. Major surgery within 28 days
  17. Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed
  18. Treatment with any investigational drug substance or experimental therapy within 4 weeks or 5 half-lives (whatever is shorter) of the substance prior to the day of apheresis
  19. Prior treatment with gene therapy products
  20. Use of checkpoint inhibitors within 5 half-lives of the respective substance
  21. Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants
  22. Pregnant or breastfeeding women
  23. Psychologic disorders, drug and/or significant active alcohol abuse
  24. Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
  25. Presence of autoantibodies against La/Sjögren syndrome (SS)-B or presence or history of autoimmune diseases
  26. Known hypersensitivity to cellular component (UniCAR02-T) and/or targeting module (TM123) excipients or to compounds of the lymphodepletion therapy or tocilizumab or corticosteroids
  27. Evidence suggesting that the patient is not likely to follow the study protocol
  28. Incapability of understanding purpose and possible consequences of the trial
  29. Patients who should not be included according to the opinion of the investigator

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: UniCAR02-T-CD123
Preconditioning (lymphodepletion) with cyclophosphamide and fludarabine, followed by combination treatment of genetically modified T-cells carrying universal chimeric antigen receptors (UniCAR02-T) with the recombinant antibody derivative TM123.
Intravenous infusion of single dose
Intravenous infusion over 3 days
Intravenous infusion over 3 days
Intravenous Infusion for 20 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase 1a Dose Escalationand Re-initiated Dose Escalation in 3+3 design: Safety and tolerability
Time Frame: DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance) until Safety Follow-up 1 (infusion period of TM123 + 28 days + 3 months)
Incidence and intensity of adverse events graded according to CTCAE V5.0 with the exception of CRS and ICANS
DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance) until Safety Follow-up 1 (infusion period of TM123 + 28 days + 3 months)
Phase 1a Dose Escalation and Re-initiated Dose Escalation in 3+3 design: Incidence of dose limiting toxicity (DLT)
Time Frame: DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)
DLT is defined as any adverse Event at least possible related to TM123 and/or UniCAR02-T
DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)
Phase 1a Dose Escalation and Re-initiated Dose Escalation in 3+3 design: Maximum tolerated dose (MTD)
Time Frame: DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)
The dose for which the isotonic estimate of the DLT probability is closest to the target DLT probability of 0.2.
DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)
Ph1b Dose Expansion: Safety and tolerability
Time Frame: Infusion period of TM123 (up to 20 days)
Incidence and intensity of adverse events graded according to CTCAE V5.0 with the exception of CRS and ICANS
Infusion period of TM123 (up to 20 days)
Ph1b Dose Expansion: Establishing recommended phase 2 dose (RP2D)
Time Frame: Infusion period of TM123 (up to 20 days)
Infusion period of TM123 (up to 20 days)
Ph1b Dose Expansion: Response evaluation
Time Frame: Infusion period of TM123 (up to 20 days)
Complete and partial remission at any time point and durability of response
Infusion period of TM123 (up to 20 days)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete (CR, CRh, CRi ) and partial remission (PR)
Time Frame: until fifteen years after last UniCAR02-T administration

CR: Bone marrow blasts < 5%, absence of extramedullary disease, absolute neutrophil count > 1 Gpt/L and platelet count > 100 Gpt/L. Level of MRD should be measured in patients achieving CR in case as suitable marker exists.

CRi: All criteria for CR except residual thrombocytopenia (platelets < 100 Gpt/L) and/or neutropenia (absolute neutrophil count < 1 Gpt/L).

PR: All hematological criteria for CR with bone marrow blasts 5-25% and decrease of pre-treatment bone marrow blast percentage by at least 50 %.

until fifteen years after last UniCAR02-T administration
Disease stabilization (DS)
Time Frame: until fifteen years after last UniCAR02-T administration
Reduction of blast percentage by 25% compared to baseline without normalization of peripheral blood counts to levels not qualifying for PR or CR.
until fifteen years after last UniCAR02-T administration
Best response rate
Time Frame: until fifteen years after last UniCAR02-T administration
The best observed response during observational period. Response states are ordered descending as follows: CR > CRi > PR > DS > refractory disease.
until fifteen years after last UniCAR02-T administration
Progression free survival (PFS)
Time Frame: until fifteen years after last UniCAR02-T administration
The time from first treatment with TM123 and UniCAR02-T until disease progression or death. If no progress of death was observed during the observational period, the patient's progression free survival time will be censored on the date the patient was last seen progression-free and alive.
until fifteen years after last UniCAR02-T administration
Overall survival (OS)
Time Frame: until fifteen years after last UniCAR02-T administration
The number of days between the first study drug administration and death from any cause. If death was not observed during the observational period, the patient's overall survival time will be censored on the date the patient was last seen alive.
until fifteen years after last UniCAR02-T administration
Toxicity and efficacy in repeated cycles of TM123 administration
Time Frame: duration of consolidation cycle treatment
Patients who tolerate TM123 and UniCAR02-T without DLT and achieve a clinical benefit are candidates for consolidation cycles
duration of consolidation cycle treatment
Establishing recommended phase 2 dose (RP2D)
Time Frame: DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)
The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.
DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Martin Wermke, MD, Universitatsklinikum Carl Gustav Carus Dresden

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 28, 2020

Primary Completion (Estimated)

May 1, 2025

Study Completion (Estimated)

September 1, 2025

Study Registration Dates

First Submitted

January 10, 2020

First Submitted That Met QC Criteria

January 14, 2020

First Posted (Actual)

January 18, 2020

Study Record Updates

Last Update Posted (Actual)

August 18, 2023

Last Update Submitted That Met QC Criteria

August 16, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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