Dose-escalating Trial With UniCAR02-T Cells and PSMA Target Module (TMpPSMA) in Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSMA Marker

April 22, 2024 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 PSMA Peptide Target Module (TMpPSMA) for the Treatment of Patients With Progressive Disease After Standard Systemic Therapy in Cancers With Positive PSMA Marker

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-pPSMA in patients with progressive disease after standard systemic therapy in castration-resistant prostate cancers with positive PSMA marker. The UniCAR02-T-pPSMA drug is a combination of a cellular component (UniCAR02-T) with a recombinant antibody derivative (TMpPSMA) which together forms the active drug.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
16

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • Germany
      • Hamburg, Germany, 20246
        • Universitätsklinikum Hamburg-Eppendorf
    • Baden-Württemberg
      • Ulm, Baden-Württemberg, Germany, 89081
        • Universitätsklinikum Ulm
    • Bayern
      • Würzburg, Bayern, Germany, 97080
        • Universitätsklinikum Würzburg
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Universitätsklinikum Dresden

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

14 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Age ≥ 18 years
  2. Patients diagnosed with progressive castration-resistant prostate cancer refractory to standard treatments and with no other available standard or curative treatment
  3. Measurable or non-measurable disease based on immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) and positivity in PSMA Positron Emission Tomography (PET)
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  5. Life expectancy of at least 3 months
  6. Adequate renal and hepatic laboratory assessments
  7. Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF)
  8. Permanent venous access existing (e.g. port-system) resp. acceptance of implantation of a device
  9. Able to give written informed consent
  10. Weight ≥ 45kg
  11. Using a highly effective method of birth control

Exclusion Criteria:

  1. Central nervous system metastasis or meningeosis carcinomatosa
  2. 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
  3. Patients undergoing renal dialysis
  4. Pulmonary disease with clinical relevant hypoxia (need for oxygen inhalation)
  5. Parkinson, epilepsy and stroke or presence or history of seizures, paresis, aphasia, central nervous system (CNS) or intracranial hemorrhage
  6. History or presence of disseminated intravascular coagulation (DIC) or thromboembolism within the last three months
  7. Multiple sclerosis
  8. Hemolytic anemia
  9. Eye diseases with neovascularization
  10. Active infectious disease considered by investigator to be incompatible with protocol or being contraindications for lymphodepletion therapy
  11. Presence of urotoxicity from previous chemo- or radiotherapy or urinary outflow obstruction
  12. Vaccination with live viruses less than 2 weeks prior lymphodepletion therapy
  13. Any disease requiring immunosuppressive therapy
  14. Major surgery within 28 days (prior start of TMpPSMA infusion)
  15. Other malignancy requiring active therapy but adjuvant endocrine therapy is allowed
  16. Treatment with any investigational drug substance or experimental therapy within 4 weeks or 5 half-lives of the substance (whatever is shorter) prior to administration of TMpPSMA
  17. Prior treatment with gene therapy products
  18. Use of checkpoint inhibitors within 5 half-lives of the respective substance prior to administration of TMpPSMA
  19. Autoimmune diseases requiring systemic steroids or other systemic immunosuppressants (note that physiologic steroid replacement not exceeding 10 mg prednisolone equivalent per day is allowed)
  20. Psychologic disorders, drug and/or significant active alcohol abuse
  21. Known history of human immunodeficiency virus (HIV) or active/chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV)
  22. Presence of autoantibodies against La/SS-B or presence or history of autoimmune diseases (e.g. systemic lupus erythematosus, SS/SLE overlap syndrome, subacute cutaneous lupus erythematosus, neonatal lupus, primary biliary cirrhosis, Sjögren's syndrome)
  23. Known hypersensitivity to cellular component (UniCAR02-T) and/or targeting peptide module (TMpPSMA) excipients and/or contraindication to compounds of the lymphodepletion therapy (cyclophosphamide and fludarabine), and tocilizumab or corticosteroids as specified in the respective IB/SmPC
  24. Evidence suggesting that the patient is not likely to follow the study protocol (e.g. lacking compliance)
  25. Incapability of understanding purpose and possible consequences of the trial
  26. 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: UniCAR02-T-pPSMA
Preconditioning (lymphodepletion) with cyclophosphamide and fludarabine, followed by combination treatment of genetically modified T-cells carrying universal chimeric antigen receptors (UniCAR02-T) with the peptide TMpPSMA.
Drug: Cyclophosphamide (Non-IMP)
Intravenous infusion for 3 days
Drug: Fludarabine (Non-IMP)
Intravenous infusion for 3 days
Drug: UniCAR02-T (IMP)
Intravenous infusion of single dose
Drug: UniCAR02-T-pPSMA
Intravenous Infusion for 21 days

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety and tolerability
Time Frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
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
DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Incidence of dose limiting toxicity (DLT)
Time Frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
DLT is defined as any adverse event at least possible related to TMpPSMA and/or UniCAR02-T
DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Maximum tolerated dose (MTD)
Time Frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
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 TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Recommended phase 2 dose (RP2D)
Time Frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
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 TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Antitumor activity
Time Frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Antitumor activity of UniCAR02-T-pPSMA at any time point according to irRECIST (immune-related) Response Evaluation Criteria in Solid Tumors): Complete remission (CR) and partial remission (PR), Objective response rate (ORR), Disease control rate (DCR), Best response rate, Duration of response (DOR),Progression free survival (PFS)
DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Prostate specific antigen (PSA) response
Time Frame: DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
DLT period (infusion period of TMpPSMA + 7 days or + 14 days in patients with with myelosuppression)
Overall Survival (OS)
Time Frame: Until fifteen years after last UniCAR02-T administration
Until fifteen years after last UniCAR02-T administration
Influence on Circulating tumor cells (CTC)
Time Frame: Before start of lymphodepletion therapy until 6 resp. 12 months after start of last TMpPSMA application
Before start of lymphodepletion therapy until 6 resp. 12 months after start of last TMpPSMA application

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AvenCell Europe GmbH

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
PHARMALOG Institut für klinische Forschung GmbH

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Ralf Bargou, Prof., Wuerzburg University Hospital

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 23, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 28, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 28, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 11, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 11, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 18, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 23, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 22, 2024

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UC02-PSMA-01
  • 2019-004211-32 (EudraCT Number)

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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