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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

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ClinicalTrials.gov Identifier: NCT04633148
Recruitment Status : Recruiting
First Posted : November 18, 2020
Last Update Posted : February 2, 2023
Sponsor:
Collaborator:
PHARMALOG Institut für klinische Forschung GmbH
Information provided by (Responsible Party):
AvenCell Europe GmbH

Tracking Information
First Submitted Date  ICMJE November 11, 2020
First Posted Date  ICMJE November 18, 2020
Last Update Posted Date February 2, 2023
Actual Study Start Date  ICMJE November 23, 2020
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 24, 2022)
  • 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
  • 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
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: November 11, 2020)
  • Safety and tolerability [ Time Frame: DLT period (infusion period of TMpPSMA + 14 days or + 21 days in patients with with myelosuppression) ]
    Incidence and intensity of adverse events graded according to CTCAE V5.0
  • Incidence of dose limiting toxicity (DLT) [ Time Frame: DLT period (infusion period of TMpPSMA + 14 days or + 21 days in patients with with myelosuppression) ]
    DLT is defined as any adverse Event at least possible related to TMpPSMA and/or UniCAR02-T
  • Maximum tolerated dose (MTD) [ Time Frame: DLT period (infusion period of TMpPSMA + 14 days or + 21 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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 24, 2022)
  • 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.
  • 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)
  • Prostate specific antigen (PSA) response [ Time Frame: 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 ]
  • Influence on Circulating tumor cells (CTC) [ Time Frame: Before start of lymphodepletion therapy until 6 resp. 12 months after start of last TMpPSMA application ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 11, 2020)
  • Recommended phase 2 dose (RP2D) [ Time Frame: DLT period (infusion period of TMpPSMA + 14 days or + 21 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.
  • Antitumor activity [ Time Frame: DLT period (infusion period of TMpPSMA + 14 days or + 21 days in patients with with myelosuppression) ]
    Antitumor activity of UniCAR02-T-pPSMA at any time point according to RECIST 1.1 (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)
  • Prostate specific antigen (PSA) response in prostate cancer [ Time Frame: DLT period (infusion period of TMpPSMA + 14 days or + 21 days in patients with with myelosuppression) ]
  • Overall Survival (OS) [ Time Frame: Until fifteen years after last UniCAR02-T administration ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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-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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Sequential Assignment
Intervention Model Description:
Dose escalation follows an adaptive design.
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Prostate Cancer
Intervention  ICMJE
  • Drug: Cyclophosphamide (Non-IMP)
    Intravenous infusion for 3 days
  • Drug: Fludarabine (Non-IMP)
    Intravenous infusion for 3 days
  • Drug: UniCAR02-T-pPSMA
    Intravenous Infusion for 21 days
  • Drug: UniCAR02-T (IMP)
    Intravenous infusion of single dose
Study Arms  ICMJE 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.
Interventions:
  • Drug: Cyclophosphamide (Non-IMP)
  • Drug: Fludarabine (Non-IMP)
  • Drug: UniCAR02-T-pPSMA
  • Drug: UniCAR02-T (IMP)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: January 24, 2022)
39
Original Estimated Enrollment  ICMJE
 (submitted: November 11, 2020)
35
Estimated Study Completion Date  ICMJE July 2024
Estimated Primary Completion Date July 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
  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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Antje Schubert, Dr. +493514466450 ext 0 UC02-PSMA-01@cellex-treatment.me
Contact: Martin Lorkowski, Dr. +493514466450 ext 0 UC02-PSMA-01@cellex-treatment.me
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04633148
Other Study ID Numbers  ICMJE UC02-PSMA-01
2019-004211-32 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party AvenCell Europe GmbH
Original Responsible Party Same as current
Current Study Sponsor  ICMJE AvenCell Europe GmbH
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE PHARMALOG Institut für klinische Forschung GmbH
Investigators  ICMJE
Principal Investigator: Ralf Bargou, Prof. Wuerzburg University Hospital
PRS Account AvenCell Europe GmbH
Verification Date January 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP