A Phase 1 interventional study of MDG1021 dose 1 and MDG1021 dose 2 in Acute Myeloid Leukemia, Acute Lymphoid Leukemia and Myelodysplastic Syndromes, sponsored by Medigene AG. Withdrawn at 1 site in Netherlands. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-10-08.
Sponsored by Medigene AG · Phase 1, Interventional, and Treatment
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.
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.
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Inclusion Criteria:
Patients (i.e. recipient) transplanted with a sibling or unrelated HSCT donor
Exclusion Criteria:
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:
Fertile men not agreeing to use effective contraceptive methods during the clinical study
Exclusion criteria at time of IMP administration:
Dose-escalation part of the study to investigate 3 MDG1021 doses. Dose-expansion part of the study to investigate the selected optimal MDG1021 dose.
Drug: MDG1021 dose 1 · Drug: MDG1021 dose 2 · Drug: MDG1021 dose 3 · Drug: MDG1021 optimal dose
3 patients to receive dose1: target dose of 0.3x10\^6 HA-1H TCR transduced T cells/kg BW ±20% in 100 mL
3 patients to receive dose 2: target dose of 1x10\^6 HA-1H TCR transduced T cells/kg BW ±20% in 100 mL
3 patients to receive dose 3: target dose of 3x10\^6 HA-1H TCR transduced T cells/kg BW +20% in 100 mL
20 patients to receive the selected optimal dose
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
Time frame: up to 28 days after T cell infusion
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)
Time frame: up to 28 days after T cell infusion
Recommended phase 2 dose (RP2D) of HA-1H TCR transduced T cells
To asses the recommended phase II dose (RP2D) of MDG1021
Time frame: up to 28 days after T cell infusion
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
Time frame: up to 28 days after T cell infusion
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)
Time frame: Up to 12 months after T cell infusion
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
Time frame: Up to 12 months after T cell infusion
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.
Time frame: Up to 12 months afterT cell infusion
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.
Time frame: Up to 12 months afterT cell infusion
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.
Time frame: Up to 12 months afterT cell infusion
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.
Time frame: Up to 12 months afterT cell infusion
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.
Time frame: Up to 12 months afterT cell infusion
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
Time frame: Up to Day 0 after T cell infusion
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
Time frame: Up to 12 months afterT cell infusion
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
Time frame: Up to 12 months afterT cell infusion
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
Time frame: Up to 12 months afterT cell infusion
Disappearance of recipient hematopoiesis (chimerism analysis) in the blood
To evaluate disappearance of recipient hematopoiesis (chimerism analysis) in the blood
Time frame: Up to 12 months after T cell infusion
Disappearance of recipient hematopoiesis (chimerism analysis) in the bone marrow
To evaluate disappearance of recipient hematopoiesis (chimerism analysis) in the bone marrow
Time frame: Up to 3 months after T cell infusion
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
Time frame: Up to 12 months after T infusion
Plan to share: No
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