- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04230265
Dose-escalating Trial With UniCAR02-T Cells and CD123 Target Module (TM123) in Patients With Hematologic and Lymphatic Malignancies
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
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Martin Lorkowski, Dr.
- Phone Number: +493514466450
- Email: UC02-123-01@avencell.com
Study Contact Backup
- Name: Antje Schubert, Dr.
- Phone Number: +493514466450
- Email: UC02-123-01@avencell.com
Study Locations
-
-
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Hamburg, Germany, 20246
- Recruiting
- Universitätsklinikum Hamburg-Eppendorf
-
Contact:
- Walter Fiedler, Prof.
- Email: fiedler@uke.de
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Baden-Württemberg
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Ulm, Baden-Württemberg, Germany, 89081
- Recruiting
- Universitätsklinikum Ulm
-
Contact:
- Elisa Sala, MD
- Email: elisa.sala@uniklinik-ulm.de
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Bavaria
-
Munich, Bavaria, Germany, 81377
- Not yet recruiting
- Klinikum der Universität München
-
Contact:
- Marion Subklewe, Prof.
- Email: Marion.Subklewe@med.uni-muenchen.de
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Bayern
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Würzburg, Bayern, Germany, 97080
- Recruiting
- Universitätsklinikum Würzburg
-
Contact:
- Sabrina Kraus, MD
- Email: kraus_s3@ukw.de
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Hessen
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Marburg, Hessen, Germany, 35032
- Recruiting
- Philipps-Universitat Marburg
-
Contact:
- Stephan Metzelder, MD
- Email: metzelde@med.uni-marburg.de
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NRW
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Aachen, NRW, Germany, 52074
- Recruiting
- UniKlinik RWTH Aachen
-
Contact:
- Edgar Jost, Prof.
- Email: ejost@ukaachen.de
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Sachsen
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Dresden, Sachsen, Germany, 01307
- Recruiting
- Universitätsklinikum Dresden
-
Contact:
- Martin Wermke, MD
- Email: martin.wermke@ukdd.de
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Principal Investigator:
- Martin Wermke, MD
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Leipzig, Sachsen, Germany, 04103
- Recruiting
- Universitätsklinikum Leipzig
-
Contact:
- Vladan Vucinic, MD
- Email: vladan.vucinic@medizin.uni-leipzig.de
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or female patients, age ≥ 18 years
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
- 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
- Permanent 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; routinely using a highly effective method of birth control
Exclusion Criteria:
- Acute promyelocytic leukemia (t15;17)
- Refractory disease under anti-leukemic treatment lasting longer than 6 months
- Manifestation of AML or BPDCN in central nervous system
- Bone marrow failure syndromes
- 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
- Patients undergoing renal dialysis
- Pulmonary disease with clinical relevant hypoxia
- Parkinson, epilepsy and, stroke or presence or history of seizures, paresis, aphasia or intracranial hemorrhage
- Presence of disseminated intravascular coagulation (DIC) or thromboembolism, or history of such within 3 months prior to start of treatment
- Hemolytic anemia
- Multiple sclerosis
- Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
- Presence of urotoxicity from previous chemo- or radiotherapy or urinary outflow obstruction
- Allogeneic stem cell transplantation within last two months or Graft versus host disease (GvHD) requiring immunosuppressive therapy
- Vaccination with live viruses less than 2 weeks prior lymphodepletion therapy
- Major surgery within 28 days
- Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed
- 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
- Prior treatment with gene therapy products
- Use of checkpoint inhibitors within 5 half-lives of the respective substance
- Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants
- Pregnant or breastfeeding women
- Psychologic disorders, drug and/or significant active alcohol abuse
- Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
- Presence of autoantibodies against La/Sjögren syndrome (SS)-B or presence or history of autoimmune diseases
- Known hypersensitivity to cellular component (UniCAR02-T) and/or targeting module (TM123) excipients or to compounds of the lymphodepletion therapy or tocilizumab or corticosteroids
- Evidence suggesting that the patient is not likely to follow the study protocol
- Incapability of understanding purpose and possible consequences of the trial
- Patients who should not be included according to the opinion of the investigator
Study Plan
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)
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DLT is defined as any adverse Event at least possible related to TM123 and/or UniCAR02-T
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DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)
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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.
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DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)
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Ph1b Dose Expansion: Safety and tolerability
Time Frame: Infusion period of TM123 (up to 20 days)
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Incidence and intensity of adverse events graded according to CTCAE V5.0 with the exception of CRS and ICANS
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Infusion period of TM123 (up to 20 days)
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Ph1b Dose Expansion: Establishing recommended phase 2 dose (RP2D)
Time Frame: Infusion period of TM123 (up to 20 days)
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Infusion period of TM123 (up to 20 days)
|
|
Ph1b Dose Expansion: Response evaluation
Time Frame: Infusion period of TM123 (up to 20 days)
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Complete and partial remission at any time point and durability of response
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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
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Disease stabilization (DS)
Time Frame: until fifteen years after last UniCAR02-T administration
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Reduction of blast percentage by 25% compared to baseline without normalization of peripheral blood counts to levels not qualifying for PR or CR.
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until fifteen years after last UniCAR02-T administration
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Best response rate
Time Frame: until fifteen years after last UniCAR02-T administration
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The best observed response during observational period.
Response states are ordered descending as follows: CR > CRi > PR > DS > refractory disease.
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until fifteen years after last UniCAR02-T administration
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Progression free survival (PFS)
Time Frame: until fifteen years after last UniCAR02-T administration
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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.
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until fifteen years after last UniCAR02-T administration
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Overall survival (OS)
Time Frame: until fifteen years after last UniCAR02-T administration
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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.
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until fifteen years after last UniCAR02-T administration
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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)
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The RP2D will be determined based on MTD, all available efficacy data, and all available safety data, including information derived from additional treatment cycles.
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DLT period (infusion period of TM123 (up to 20 days) + 7 days or + 14 days in patients with complete blast clearance)
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Martin Wermke, MD, Universitatsklinikum Carl Gustav Carus Dresden
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
- Fludarabine
Other Study ID Numbers
- UC02-123-01
- 2019-001339-30 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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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