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

NCT03503968 | Terminated Phase 1 DMC

• 1 other identifier: CD-TCR-001
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 9

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).

Conditions

Safety; Tolerability; Feasibility; Treatment Efficacy

Outcome Measures

Primary Outcomes (5)

• Phase I: Adverse Events and Dose Limiting Toxicities (Safety and Tolerability)

  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

  3 months

• Phase I: maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of MDG101

  28 days

• Phase I: For feasibility: percent of all subjects who receive the planned target dose of MDG1011

  3 months

• Phase II: Adverse Events (Safety)

  Incidence and severity of adverse events according to NCI CTCAE, v4.03

  3 months

• Phase II: overall response rate (ORR)

  3 months

Secondary Outcomes (20)

• 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 I: time to event and time to progression (TTP) 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

Study Arms (5)

Phase I - 3 disease entities

EXPERIMENTAL

MDG1011 administration of escalating doses

Drug: MDG1011

Phase II - HLA*02:01 - disease entity 1

EXPERIMENTAL

MDG1011 administration of Phase II recommended dose

Drug: MDG1011

Phase II - HLA*other - disease entity 1

ACTIVE COMPARATOR

Investigator Choice therapy

Other: Investigator Choice therapy

Phase II - HLA*02:01 - disease entity 2

EXPERIMENTAL

MDG1011 administration of Phase II recommended dose

Drug: MDG1011

Phase II - HLA*other - disease entity 2

ACTIVE COMPARATOR

Investigator Choice therapy

Other: Investigator Choice therapy

Interventions

MDG1011 DRUG

PRAME-T-Cell Receptor Gene Modified Autologous T Cells

Phase I - 3 disease entities; Phase II - HLA*02:01 - disease entity 1; Phase II - HLA*02:01 - disease entity 2

Investigator Choice therapy OTHER

Any intervention/therapy chosen by the investigator

Phase II - HLA*other - disease entity 1; Phase II - HLA*other - disease entity 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written informed consent prior to any clinical trial-related activities
• Documented diagnosis with the last disease staging within the last 4 weeks prior to screening
• Human leukocyte antigen (HLA):
• Phase I and Phase II (treatment group): Subjects positive for HLA-A\*02:01 according to genotyping results
• Phase II (concurrent control group): Subjects negative for HLA-A\*02:01 according to genotyping results
• Age ≥ 18 years
• Life expectancy of at least 4 months.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Subjects not planned for allogeneic HSCT (e.g. based on disease characteristics or subject characteristics). Bridging to an allogeneic HSCT will be allowed.
• Females of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-hCG) pregnancy test result before leukapheresis and before administration of lymphodepleting chemotherapy. Females of non-childbearing potential are those who are postmenopausal greater than 2 years or who have had a bilateral tubal ligation or hysterectomy.
• Females of childbearing potential and males who have partners of childbearing potential must agree to use an effective contraception method during the clinical trial and for 6 months following the last dose of IMP.
• Effective birth control includes:
• intrauterine device plus 1 barrier method; or (b) 2 barrier methods. Effective barrier methods are male or female condoms, diaphragms, and spermicides (creams or gels that contain a chemical to kill sperm).
• No Complete remission/response (CR) or Complete remission with incomplete hematologic recovery (CRi) after completion of at least 2 cycles of intensive induction chemotherapy or 1 cycle of intensive induction and consolidation (intermediate or high dose cytarabine) chemotherapy each and/or
• No CR or no CRi after completion of at least 1 cycle of intensive induction chemotherapy including at least 5 days of cytarabine 100-200 mg/m\^2 continuously or an equivalent regimen with cytarabine with total dose not less than 500 mg/m\^2 per cycle and at least 2 days of an anthracycline (e.g. daunorubicine, idarubicin), unable to undergo allogeneic HSCT and/or

You may not qualify if:

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• Subjects with acute promyelocytic leukemia exhibiting t(15;17)(q22;q12); PML-RARA, or with variant translocations
• Pregnant or lactating women
• Known positive for HIV, active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
• Any clinically significant, advanced or unstable disease or inadequate main organ function that may put the subject at special risk, such as: a. creatinine \> 2.0 times the upper normal serum level b. total bilirubin, ALT, AST \>3 times the upper normal serum level c. cardiac left ventricular ejection fraction \< 40% at rest d. severe restrictive or obstructive lung disease
• History of haploidentical allogeneic stem cell transplantation
• Subjects both with urinary outflow obstructions and on dialysis or subjects for whom cyclophosphamide is contraindicated for other reasons
• Clinical significant and ongoing immune suppression including, but not limited to: immunosuppressive agents such as cyclosporine or corticosteroids (at an equivalent dose of \>= 10 mg prednisone per day). Inhaled steroid and physiological replacement for adrenal insufficiency is allowed.
• Subjects with currently active autoimmune disease.
• Subjects with a history of primary immunodeficiency.
• Subjects with a currently active second malignancy other than non- melanoma skin cancers or subjects with history of prior malignancy and previously treated with a curative intent therapy less than 1 year ago
• Known or suspected hypersensitivity or intolerance to IMP, cyclophosphamide, fludarabine and/or tocilizumab or to any of the excipients
• Participation in any clinical trial \< 60 days prior to first IMP administration in case of antibodies and \< 14 days for all other IMPs
• Vulnerable subjects and/or subjects unwilling or unable to comply with procedures required in this clinical trial protocol
• Prior therapy with IMiDs within 14 days prior to leukapheresis and/or infusion of IMP

Sponsors & Collaborators

• Medigene AG: lead

Study Sites (9)

University Hospital Dresden

Dresden, Germany

Location

University Hospital Erlangen

Erlangen, Germany

Location

University Hospital Frankfurt

Frankfurt, Germany

Location

University Hospital Freiburg

Freiburg im Breisgau, Germany

Location

University Hospital Heidelberg

Heidelberg, Germany

Location

University Hospital Leipzig

Leipzig, Germany

Location

University Hospital Mainz

Mainz, Germany

Location

University Hospital Regensburg

Regensburg, Germany

Location

University Hospital Wuerzburg

Würzburg, Germany

Location

Related Publications (1)

• Burdek M, Prinz PU, Mutze K, Tippmer S, Geiger C, Longinotti G, Schendel DJ. Characterization of a 3S PRAME VLD-Specific T Cell Receptor and Its Use in Investigational Medicinal Products for TCR-T Therapy of Patients with Myeloid Malignancies. Cancers (Basel). 2025 Jan 13;17(2):242. doi: 10.3390/cancers17020242.

  PMID: 39858024 DERIVED

Study Officials

• Simone Thomas, PD Dr. med.

  University Hospital Regensburg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2018
• First Posted: April 20, 2018
• Study Start: March 27, 2018
• Primary Completion: June 28, 2022
• Study Completion: July 15, 2022
• Last Updated: February 15, 2023

Record last verified: 2023-02

Locations

DE (9)