TCR Modified T Cells MDG1011 in High Risk Myeloid and Lymphoid Neoplasms

Phase 1

Terminated

• Conditions: Safety; Tolerability; Feasibility; Treatment Efficacy
• Interventions: Drug: MDG1011; Other: Investigator Choice therapy

• Registration Number: NCT03503968
• Lead Sponsor: Medigene AG

Brief Summary

This is a multicentre, non-randomized, open-label, Phase I/II clinical trial of MDG1011, an investigational medicinal product (IMP), consisting of patient-derived autologous T cells, persistently transduced with a Preferentially Expressed Antigen in Melanoma (PRAME)-specific human leukocyte antigen (HLA)-A\*02:01-restricted T cell receptor (TCR).

Detailed Description

Phase I:

The Phase I dose escalation part will establish the MTD/RP2D in subjects with high risk myeloid and lymphoid neoplasms, a total of 3 disease entities.

Phase I subjects will be enrolled into the following cohorts and treated with a single intravenous (i.v.) infusion of IMP:

* Cohort 1: target dose of 1 x 105 T cells/kg ± 20%

* Cohort 2: target dose of 1 x 106 T cells/kg ± 20%

* Cohort 3: target dose of 5 x 106 T cells/kg ± 20%

* Optional cohort 4: up to 1 x 107 T cells/kg + 20%

Phase II:

The Phase II part consists of two arms, each representing one disease entity. Within each arm, representing a disease entity, subjects will be enrolled in 2 different treatment groups to receive either:

1. IMP in the treatment group (up to 20 subjects who are positive for human leukocyte antigen (HLA)-A\*02:01); Or

2. therapy as per Investigator's discretion in the concurrent control (up to 20 subjects who are negative for HLA-A\*02:01).

Study Timeline

• Study First Submitted: 2018-03-21
• Study Start: 2018-03-27
• Study First Submitted QC: 2018-04-11
• Study First Posted: 2018-04-20
• Primary Completion: 2022-06-28
• Study Completion: 2022-07-15
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-13
• Last Update Posted: 2023-02-15

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

Not provided

Read More

Exclusion Criteria

Not provided

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Phase II - HLA*02:01 - disease entity 2	MDG1011	MDG1011 administration of Phase II recommended dose
Phase I - 3 disease entities	MDG1011	MDG1011 administration of escalating doses
Phase II - HLA*02:01 - disease entity 1	MDG1011	MDG1011 administration of Phase II recommended dose
Phase II - HLA*other - disease entity 1	Investigator Choice therapy	Investigator Choice therapy
Phase II - HLA*other - disease entity 2	Investigator Choice therapy	Investigator Choice therapy

Primary Outcome Measures

Name	Time	Method
Phase I: For feasibility: percent of all subjects who receive the planned target dose of MDG1011	3 months
Phase II: overall response rate (ORR)	3 months
Phase I: maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of MDG101	28 days
Phase II: Adverse Events (Safety)	3 months	Incidence and severity of adverse events according to NCI CTCAE, v4.03
Phase I: Adverse Events and Dose Limiting Toxicities (Safety and Tolerability)	3 months	Incidence and severity of adverse events according to the NCI CTCAE, v4.03; MTD and/or RP2D of IMP measured by dose-limiting toxicities (DLTs) up to 28 days post infusion

Secondary Outcome Measures

Name	Time	Method
Phase I: overall response rate (ORR)	3, 6 and 12 months
Phase I: time to event and duration of response (DoR) rate	3, 6 and 12 months
Phase II: changes in quality of life (QoL)	baseline, 3, 6 and 12 months	EORTC-MY20 \[MM\] questionaire
Phase I: Correlation of PRAME expression with the antitumor response	3, 6 and 12 months
Phase II: time to event and duration of response (DoR) rate	3, 6 and 12 months
Phase II: time to event and time to progression (TTP) rate	3, 6 and 12 months
Phase II: time to event and progression-free survival (PFS) rate	3, 6 and 12 months
Phase II: For feasibility, the percent of all subjects who receive the RP2D of MDG1011	3 months
Phase II: correlation of PRAME expression with the antitumor response	3, 6 and 12 months
Phase I: Adverse Events (safety)	6 and 12 months	Incidence and severity of adverse events according to NCI CTCAE, v4.03
Phase II: Adverse Events (safety)	6 and 12 months	Incidence and severity of adverse events according to NCI CTCAE, v4.03
Phase I: time to event and time to progression (TTP) rate	3, 6 and 12 months
Phase II: time to event and overall survival (OS) rate	3, 6 and 12 months
Phase I: time to event and progression-free survival (PFS) rate	3, 6 and 12 months
Phase I: time to event and overall survival (OS) rate	3, 6 and 12 months
Phase I: Change in quality of life (QoL)	baseline, 3, 6 and 12 months	EORTC-MY20 \[MM\] questionaire

Trial Locations

Locations (9)

University Hospital Erlangen; 🇩🇪 Erlangen, Germany

University Hospital Freiburg; 🇩🇪 Freiburg, Germany

University Hospital Mainz; 🇩🇪 Mainz, Germany

University Hospital Dresden; 🇩🇪 Dresden, Germany

University Hospital Frankfurt; 🇩🇪 Frankfurt, Germany

University Hospital Heidelberg; 🇩🇪 Heidelberg, Germany

University Hospital Leipzig; 🇩🇪 Leipzig, Germany

University Hospital Regensburg; 🇩🇪 Regensburg, Germany

University Hospital Wuerzburg; 🇩🇪 Wuerzburg, Germany