Clinical Trials Logo

Clinical Trial Details — Status: Withdrawn

Administrative data

NCT number NCT04464889
Other study ID # CD-TCR-003
Secondary ID
Status Withdrawn
Phase Phase 1
First received
Last updated
Start date July 2, 2020
Est. completion date July 2025

Study information

Verified date September 2021
Source Medigene AG
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a non-randomised, open-label phase I study of an investigational medicinal product (IMP) consisting of a HLA-A*02:01 restricted HA-1H T cell receptor transduced T cell (MDG1021) immunotherapy for relapsed or persistent hematologic malignancies after allogeneic hematopoietic stem cell transplantation. The aim of the study is to determine the recommended phase II dose of MDG1021.


Description:

This phase I is designed to assess the safety and feasibility of a HLA-A*02:01 restricted, HA-1H T cell receptor (TCR) transduced patient-derived T cell (MDG1021) immunotherapy, with secondary endpoints including preliminary efficacy, in patients with relapsed or persistent hematologic malignancies after allogeneic hematopoietic stem cell transplantation. In the dose-escalation part of the study, at least 9 patients will be treated with MDG1021 at 3 different doses to assess the safety and the maximum tolerated dose using a standard 3+3 cohort design. Thereafter, the selected optimal MDG1021 dose will be assessed for safety and preliminary efficacy in 20 additional patients during the dose-expansion part of the study. Manufacturing feasibility will be determined. MDG1021 will be administered by single intravenous infusion. HA-1H is exclusively expressed on cells of the hematopoietic system. If the patient's blood-cells, and thus lymphoma or leukemic cells, carry the immunogenic version of the HA-1H antigen on their surface and the donor stem cells do not, MDG1021 immunotherapy could eradicate the patient's cancer cells and allow the donor stem cells to repopulate the patient's blood forming system.


Recruitment information / eligibility

Status Withdrawn
Enrollment 0
Est. completion date July 2025
Est. primary completion date July 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: 1. Relapsed or persistent disease is defined according to disease specific guidelines (AML, CML, MM, ALL, MDS, MPN, MF and malignant B- or T-cell lymphoma) and includes MRD positivity. 2. Patients positive for HLA-A*02:01 according to genotyping results 3. Patients positive for HA-1H 4. Patients who received the allo-HSCT at least 100 days preceding the leukapheresis 5. Patients (i.e. recipient) transplanted with a sibling or unrelated HSCT donor 1. donor being HLA-A*02:01 positive and HA-1H negative, or 2. a donor with a single mismatch at HLA-A*02:01, being HA-1H positive or negative 6. Patients from whom at least 10x10^6 donor CD8+ T cells can be harvested by leukapheresis 7. Age = 18 years, of either sex 8. ECOG performance status 0-2. 9. Life expectancy of at least 3 months 10. Patients must be able to understand and be willing to give signed informed consent Exclusion Criteria: 1. Evidence of acute or chronic graft versus host disease (GVHD) = grade II 2. Serologic evidence of acute or chronic hepatitis B virus infection (i.e. positive for HBsAg or IgM anti-HBc). Positive HIV and HCV serology or active bacterial infection 3. Medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the investigator. Special risks to be considered: 1. Creatinine > 2.5 times the upper limit of normal (ULN) serum level 2. Total bilirubin, ALAT, ASAT > 3.0 x ULN serum level 3. Cardiac left ventricular ejection fraction < 35% at rest 4. Severe restrictive or obstructive lung disease 4. Clinically significant and ongoing immune suppression including, but not limited to immunosuppressive agents (e.g. cyclosporine or corticosteroids (at an equivalent dose of = 10 mg prednisone per day)). Inhaled steroid and physiological replacement for adrenal insufficiency is allowed 5. Patients with a history of primary immunodeficiency 6. Patients with a currently active second malignancy other than nonmelanoma skin cancers or subjects with history of prior malignancy and previously treated with a curative intent therapy less than 1 year ago 7. Patients both with urinary outflow obstructions and on dialysis or patients for whom cyclophosphamide is contraindicated for other reasons 8. Known or suspected hypersensitivity or intolerance to IMP, cyclophosphamide, fludarabine and/or tocilizumab or to any of the excipients 9. Participation in any clinical study < 60 days prior to first IMP administration in case of antibodies and < 14 days for all other IMPs 10. Vulnerable patients and/or patients unwilling or unable to comply with procedures required in this clinical study protocol 11. Pregnant or lactating women 12. Women of child-bearing potential not using highly effective method(s) of birth control (i.e., with low failure rate < 1% per year) throughout the study and/or unwilling to be tested for pregnancy. A negative serum ß-hCG test is required at baseline 13. Fertile men not agreeing to use effective contraceptive methods during the clinical study Exclusion criteria at time of IMP administration: 14. Uncontrolled central nervous system (CNS) disease 15. Uncontrolled, life threatening infections or uncontrolled disseminated intravascular coagulation; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule 16. Evidence of acute or chronic graft versus host disease (GVHD) = grade II 17. Unable to generate HA-1H TCR transduced T cells for transfusion (out of specification). However, if a lower than planned number of cells is available, the patient will have the option to receive the OOS HA-1H TCR transduced T cells product (cell dose must be at least the lowest dose level of D1 and will be analyzed in the safety and full analysis set populations. 18. If not enough starting material is collected during leukapheresis, the patient will be excluded from study participation and receive best available standard therapy.

Study Design


Intervention

Drug:
MDG1021 dose 1
3 patients to receive dose1: target dose of 0.3x10^6 HA-1H TCR transduced T cells/kg BW ±20% in 100 mL
MDG1021 dose 2
3 patients to receive dose 2: target dose of 1x10^6 HA-1H TCR transduced T cells/kg BW ±20% in 100 mL
MDG1021 dose 3
3 patients to receive dose 3: target dose of 3x10^6 HA-1H TCR transduced T cells/kg BW +20% in 100 mL
MDG1021 optimal dose
20 patients to receive the selected optimal dose

Locations

Country Name City State
Netherlands Leiden University Medical Centre Leiden Zuid Holland

Sponsors (1)

Lead Sponsor Collaborator
Medigene AG

Country where clinical trial is conducted

Netherlands, 

Outcome

Type Measure Description Time frame Safety issue
Other Feasibility of manufacturing HA-1H TCR transducer T cells: proportion of patients for whom leukapheresis was feasible Feasibility is determined by the proportion of patients for whom leukapheresis was feasible, for whom manufacturing MDG1021 was feasible, and whom received MDG1021 by intravenous infusion Up to Day 0 after T cell infusion
Other Persistence and expansion of HA-1H transduced T cells in peripheral blood To evaluate the persistence (flow cytometry with tetramers evaluating the % HA-1H transduced T cells among all T cells) and expansion of HA-1H transduced T cells (as % HA-1H transduced T cells among all T cells over time) in peripheral blood Up to 12 months afterT cell infusion
Other Function of HA-1H TCR transduced T cells detectable in peripheral blood To evaluate the function of HA-1H TCR transduced T cells detectable in peripheral blood by ELISA, measuring Interferon gamma production Up to 12 months afterT cell infusion
Other Phenotype of HA-1H TCR transduced T cells detectable in peripheral blood To evaluate the phenotype of HA-1H TCR transduced T cells detectable in peripheral blood by flow cytometry of T cell subtypes expressed in % of all T cells Up to 12 months afterT cell infusion
Other Disappearance of recipient hematopoiesis (chimerism analysis) in the blood To evaluate disappearance of recipient hematopoiesis (chimerism analysis) in the blood Up to 12 months after T cell infusion
Other Disappearance of recipient hematopoiesis (chimerism analysis) in the bone marrow To evaluate disappearance of recipient hematopoiesis (chimerism analysis) in the bone marrow Up to 3 months after T cell infusion
Other Other explorative endpoints To investigate biomarkers and molecular signatures, potentially related to safety, anti-tumor activity, the mode-of-action of MDG1021 and the pathophysiology of disease Up to 12 months after T infusion
Primary Safety and tolerability of HA-1H TCR transduced T cells: incidence and severity of adverse events To assess the incidence and severity of adverse events during the dose escalation part of the study according to the NCI CTCAE v5.0 up to 28 days after T cell infusion
Primary Maximum tolerated dose (MTD) of HA-1H TCR transduced T cells To asses the maximum tolerated dose (MTD) of MDG1021 as determined by dose-limiting toxicities (DLTs) up to 28 days after T cell infusion
Primary Recommended phase 2 dose (RP2D) of HA-1H TCR transduced T cells To asses the recommended phase II dose (RP2D) of MDG1021 up to 28 days after T cell infusion
Primary Safety and tolerability of HA-1H TCR transduced T cells at recommended phase II dose: incidence and severity of adverse events To assess the incidence and severity of adverse events of MDG1021 at the RP2D during the expansion part of the study according to the NCI CTCAE v5.0 up to 28 days after T cell infusion
Secondary Safety and tolerability (both parts of the study): incidence and severity of adverse events To assess the incidence and severity of AEs = grade 3 (NCI CTCAE v5.0) Up to 12 months after T cell infusion
Secondary Overall response rate To assess the overall response rate defined as the proportion of patients with a best overall response of complete response (CR), partial response (PR), and/or their disease specific subcategories Up to 12 months after T cell infusion
Secondary Overall survival To assess the overall survival (OS) defined as the time from the date of signing the informed consent until the documented date of death. Up to 12 months afterT cell infusion
Secondary Progression free survival To assess the progression-free survival (PFS) defined as the time from the date of signing the date of signed informed consent until progressive disease/relapse or death, whichever occurs first. Up to 12 months afterT cell infusion
Secondary Duration of response To assess the duration of response (DoR) defined as time from the date of the first documented response to the first documented progression of disease or death due to underlying cancer. Up to 12 months afterT cell infusion
Secondary Quality of life (EQ-5D-5L) The quality of life will be assessed by using the EQ-5D-5L questionnaire, consisting of 5 questions. Higher scores correspond to higher quality of life. Up to 12 months afterT cell infusion
Secondary Quality of life (VAS) The quality of life will be assessed by a visual analog scale (EuroQoL), having a range of 0 ot 100, with higher scores corresponding to better quality of life. Up to 12 months afterT cell infusion
See also
  Status Clinical Trial Phase
Recruiting NCT05027594 - Ph I Study in Adult Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02412878 - Once-weekly Versus Twice-weekly Carfilzomib in Combination With Dexamethasone in Adults With Relapsed and Refractory Multiple Myeloma Phase 3
Completed NCT01947140 - Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies Phase 1/Phase 2
Recruiting NCT05971056 - Providing Cancer Care Closer to Home for Patients With Multiple Myeloma N/A
Recruiting NCT05243797 - Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation Phase 3
Active, not recruiting NCT04555551 - MCARH109 Chimeric Antigen Receptor (CAR) Modified T Cells for the Treatment of Multiple Myeloma Phase 1
Recruiting NCT05618041 - The Safety and Efficay Investigation of CAR-T Cell Therapy for Patients With Hematological Malignancies N/A
Active, not recruiting NCT03844048 - An Extension Study of Venetoclax for Subjects Who Have Completed a Prior Venetoclax Clinical Trial Phase 3
Recruiting NCT03412877 - Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Neoantigens in People With Metastatic Cancer Phase 2
Completed NCT02916979 - Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG Phase 1
Recruiting NCT03570983 - A Trial Comparing Single Agent Melphalan to Carmustine, Etoposide, Cytarabine, and Melphalan (BEAM) as a Preparative Regimen for Patients With Multiple Myeloma Undergoing High Dose Therapy Followed by Autologous Stem Cell Reinfusion Phase 2
Completed NCT03665155 - First-in- Human Imaging of Multiple Myeloma Using 89Zr-DFO-daratumumab, a CD38-targeting Monoclonal Antibody Phase 1/Phase 2
Terminated NCT03399448 - NY-ESO-1-redirected CRISPR (TCRendo and PD1) Edited T Cells (NYCE T Cells) Phase 1
Completed NCT02812706 - Isatuximab Single Agent Study in Japanese Relapsed AND Refractory Multiple Myeloma Patients Phase 1/Phase 2
Active, not recruiting NCT05024045 - Study of Oral LOXO-338 in Patients With Advanced Blood Cancers Phase 1
Active, not recruiting NCT03792763 - Denosumab for High Risk SMM and SLiM CRAB Positive, Early Myeloma Patients Phase 2
Active, not recruiting NCT03989414 - A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Treatments in Participants With Relapsed or Refractory Multiple Myeloma (RRMM) and Newly Diagnosed Multiple Myeloma (NDMM) Phase 1/Phase 2
Withdrawn NCT03608501 - A Study of Ixazomib, Thalidomide and Dexamethasone in Newly Diagnosed and Treatment-naive Multiple Myeloma (MM) Participants Non-eligible for Autologous Stem-cell Transplantation Phase 2
Recruiting NCT04537442 - Clinical Study to Evaluate the Safety and Efficacy of IM21 CAR-T Cells in the Treatment of Elderly Patients With Relapsed or Refractory Multiple Myeloma Phase 1
Completed NCT02546167 - CART-BCMA Cells for Multiple Myeloma Phase 1