Dose-escalating Trial With UniCAR02-T Cells and CD123 Target Module (TM123) in Patients With Hematologic and Lymphatic Malignancies
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|ClinicalTrials.gov Identifier: NCT04230265|
Recruitment Status : Recruiting
First Posted : January 18, 2020
Last Update Posted : January 14, 2022
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia (AML)||Drug: Cyclophosphamide (Non-IMP) Drug: Fludarabine (Non-IMP) Drug: TM123 (IMP) Drug: UniCAR02-T (IMP)||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||45 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||Dose escalation follows an adaptive design.|
|Masking:||None (Open Label)|
|Official Title:||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|
|Actual Study Start Date :||January 28, 2020|
|Estimated Primary Completion Date :||December 2022|
|Estimated Study Completion Date :||June 2023|
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.
Drug: Cyclophosphamide (Non-IMP)
Intravenous infusion for 3 days
Drug: Fludarabine (Non-IMP)
Intravenous infusion for 3 days
Drug: TM123 (IMP)
Intravenous Infusion for 21 days
Drug: UniCAR02-T (IMP)
Intravenous infusion of single dose
- Safety and tolerability [ Time Frame: DLT period (infusion period of TM123 + 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
- Incidence of dose limiting toxicity (DLT) [ Time Frame: DLT period (infusion period of TM123 + 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
- Maximum tolerated dose (MTD) [ Time Frame: DLT period (infusion period of TM123 + 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.
- Establishing recommended phase 2 dose (RP2D) [ Time Frame: DLT period (infusion period of TM123 + 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.
- 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 %.
- 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.
- 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.
- 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.
- 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.
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04230265
|Contact: Martin Lorkowski, Dr.||+493514466450 ext 0||UC02email@example.com|
|Contact: Antje Schubert, Dr.||+493514466450 ext 0||UC02firstname.lastname@example.org|
|Ulm, Baden-Württemberg, Germany, 89081|
|Contact: Elisa Sala, MD email@example.com|
|Würzburg, Bayern, Germany, 97080|
|Contact: Sabrina Kraus, MD firstname.lastname@example.org|
|Marburg, Hessen, Germany, 35032|
|Contact: Stephan Metzelder, MD email@example.com|
|Dresden, Sachsen, Germany, 01307|
|Contact: Martin Wermke, MD firstname.lastname@example.org|
|Principal Investigator: Martin Wermke, MD|
|Leipzig, Sachsen, Germany, 04103|
|Contact: Vladan Vucinic, MD email@example.com|
|Hamburg, Germany, 20246|
|Contact: Walter Fiedler, Prof. firstname.lastname@example.org|
|Principal Investigator:||Martin Wermke, MD||Universitätsklinikum Carl Gustav Carus Dresden|