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SafetyPhase 1/2NCT03503968

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

A Phase 1/2 study testing MDG1011 and Investigator Choice therapy in people with Safety and Tolerability, run by Medigene AG at 9 sites in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Safety, Tolerability, Feasibility
What is being tested?
MDG1011 and Investigator Choice therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
9 sitesGermany
Study dates
27 Mar 2018to 15 Jul 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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).
  • AML-SPECIFIC INCLUSION CRITERIA:
  • 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
  • Refractory disease (including stable disease [SD], progressive disease [PD]) or relapsed disease after hypomethylating agent therapy (e.g. azacitidine, decitabine) and/or
  • Any SD, partial response (PR), CRi, CR obtained after re-induction or salvage-therapy and/or
  • Relapsed AML patients unable to undergo allogeneic HSCT and/or
  • Relapsed AML after allogeneic HSCT
  • at least 100 days after transplant
  • no evidence of active acute or chronic GvHD at enrolment
  • in case of history of acute (> overall grade 1) or chronic GvHD (moderate/severe) requiring immunosuppression treatment, no immunosuppression within the last 3 months
  • no immunosuppression (with the exception of low dose steroids <= 10 mg prednisone or equivalent) 4 weeks before enrolment and ongoing and
  • Myeloid blasts must positively express PRAME
  • MDS-SPECIFIC INCLUSION CRITERIA:
  • IPSS INT-2 or High Grade MDS Excess Blasts-2 (EB-2) not responding to at least 6 courses of azacitidine or 4 courses of decitabine and/or
  • IPSS INT-1, INT-2 or High Grade MDS with recurrence after initial response and
  • Blasts must positively express PRAME
  • MM-SPECIFIC INCLUSION CRITERIA:
  • Relapsed and refractory multiple myeloma:
  • Progressive MM, also defined as relapsed disease, defined as:
  • A 25% increase from baseline in the serum M-protein (absolute increase
  • 0.5 g/dL), urine M-protein (absolute increase > 200 mg/day), and/or the difference between involved and uninvolved free light chain levels (absolute increase ≥ 10 mg/dL).
  • The presence of definite new bone lesions and/or soft tissue plasmacytomas with a clear increase in the size of existing plasmacytomas, or hypercalcemia, that cannot be attributed to another cause. • Relapsed and refractory MM is defined as disease progression within 60 days of a patient's last treatment where at least a minimal response was achieved. • Primary refractory MM is defined as disease that fails to achieve at least a minimal response with any therapy. and
  • At least 3 previous therapy lines with at least one proteasome inhibitor and one immunomodulatory derivate (IMiDs). Induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen. and
  • Myeloma cells must positively express PRAME
  • CRITERIA FOR PRE-EMPTIVE LEUKAPHERESIS PROCEDURE
  • subject is positive for HLA-A*02:01 and their blasts/myeloma cells express PRAME
  • subject fulfills at least some inclusion criteria and, based on the judgement of the investigator, have a likelihood of being eligible for IMP administration in the further course of the subjects disease
  • subject does not fulfill any exclusion criterion that would be considered permanent (i.e.
  • irreversible organ function impairment) and therefore would certainly preclude the subject from receiving the IMP in the future

Who cannot join

  • <!-- -->
  • 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
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  • 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
  • MM-SPECIFIC EXCLUSION CRITERIA FOR PHASE I AND PHASE II (TREATMENT GROUP):
  • Prior therapy with IMiDs within 14 days prior to leukapheresis and/or infusion of IMP
  • Prior therapy with corticosteroids within 7 days prior to leukapheresis or 7 days prior to infusion of IMP
  • EXCLUSION CRITERIA FOR TREATMENT WITH IMP IN PHASE I AND PHASE II (TREATMENT GROUP):
  • Uncontrolled central nervous system (CNS) disease
  • Uncontrolled infections or uncontrolled disseminated intravascular coagulation; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule
  • Ongoing 3 grade cardiac, renal, pulmonary, gastrointestinal or hepatic toxicities according to CTCAE v4.03; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule
  • Evidence of acute or chronic GvHD

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

Germany9 sites

  • University Hospital Dresden

    Dresden

  • University Hospital Erlangen

    Erlangen

  • University Hospital Frankfurt

    Frankfurt

  • University Hospital Freiburg

    Freiburg im Breisgau

  • University Hospital Heidelberg

    Heidelberg

  • University Hospital Leipzig

    Leipzig

  • University Hospital Mainz

    Mainz

  • University Hospital Regensburg

    Regensburg

  • University Hospital Wuerzburg

    Würzburg

Other trials in Germany

About this study

Official title: A Phase I/II, Open-Label, Non-Randomized, Multicentre, Dose-Escalation Clinical Trial With Control Group to Evaluate the Safety, Feasibility and Preliminary Efficacy of PRAME TCR Modified T Cells, MDG1011, in Subjects With High Risk Myeloid and Lymphoid Neoplasms

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).

Read the 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).
Being tested
MDG1011, Investigator Choice therapy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MDG1011Drug

    PRAME-T-Cell Receptor Gene Modified Autologous T Cells

  • Investigator Choice therapyOther

    Any intervention/therapy chosen by the investigator

Study groups in NCT03503968
Study groupRoleWhat they receive
Phase I - 3 disease entitiesExperimentalMDG1011 administration of escalating doses
Receives: Drug: MDG1011
Phase II - HLA*02:01 - disease entity 1ExperimentalMDG1011 administration of Phase II recommended dose
Receives: Drug: MDG1011
Phase II - HLA*other - disease entity 1Active comparatorInvestigator Choice therapy
Receives: Other: Investigator Choice therapy
Phase II - HLA*02:01 - disease entity 2ExperimentalMDG1011 administration of Phase II recommended dose
Receives: Drug: MDG1011
Phase II - HLA*other - disease entity 2Active comparatorInvestigator Choice therapy
Receives: Other: Investigator Choice therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 3 months

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

    Measured: 28 days

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

    Measured: 3 months

  4. Phase II: Adverse Events (Safety)

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

    Measured: 3 months

  5. Phase II: overall response rate (ORR)

    Measured: 3 months

Secondary outcomes (20)

  1. Phase I: overall response rate (ORR)

    Measured: 3, 6 and 12 months

  2. Phase I: time to event and duration of response (DoR) rate

    Measured: 3, 6 and 12 months

  3. Phase I: time to event and time to progression (TTP) rate

    Measured: 3, 6 and 12 months

  4. Phase I: time to event and progression-free survival (PFS) rate

    Measured: 3, 6 and 12 months

  5. Phase I: time to event and overall survival (OS) rate

    Measured: 3, 6 and 12 months

  6. Phase I: Change in quality of life (QoL)

    EQ-5D-5L questionaire

    Measured: baseline, 3, 6 and 12 months

  7. Phase I: Change in quality of life (QoL)

    EORTC-QLQ-C30 [AML/MDS] questionaire

    Measured: baseline, 3, 6 and 12 months

  8. Phase I: Change in quality of life (QoL)

    EORTC-MY20 [MM] questionaire

    Measured: baseline, 3, 6 and 12 months

  9. Phase I: Correlation of PRAME expression with the antitumor response

    Measured: 3, 6 and 12 months

  10. Phase II: time to event and duration of response (DoR) rate

    Measured: 3, 6 and 12 months

  11. Phase II: time to event and time to progression (TTP) rate

    Measured: 3, 6 and 12 months

  12. Phase II: time to event and progression-free survival (PFS) rate

    Measured: 3, 6 and 12 months

  13. Phase II: time to event and overall survival (OS) rate

    Measured: 3, 6 and 12 months

  14. Phase II: changes in quality of life (QoL)

    EQ-5D-5L questionaire

    Measured: baseline, 3, 6 and 12 months

  15. Phase II: changes in quality of life (QoL)

    EORTC-QLQ-C30 [AML/MDS] questionaire

    Measured: baseline, 3, 6 and 12 months

  16. Phase II: changes in quality of life (QoL)

    EORTC-MY20 [MM] questionaire

    Measured: baseline, 3, 6 and 12 months

  17. Phase II: For feasibility, the percent of all subjects who receive the RP2D of MDG1011

    Measured: 3 months

  18. Phase II: correlation of PRAME expression with the antitumor response

    Measured: 3, 6 and 12 months

  19. Phase I: Adverse Events (safety)

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

    Measured: 6 and 12 months

  20. Phase II: Adverse Events (safety)

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

    Measured: 6 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Apr 2018
  2. Study start27 Mar 2018
  3. Primary completion28 Jun 2022
  4. Study completion15 Jul 2022

Why it stopped: The clinical trial is terminated after the completion of phase I without moving to Phase II.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03503968
Sponsor's protocol ID
CD-TCR-001
Status last verified
Feb 2023
First submitted
21 Mar 2018
Last updated
15 Feb 2023
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 39858024

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing MDG1011 and Investigator Choice therapy in people with Safety and Tolerability, run by Medigene AG at 9 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 42 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 15 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: The clinical trial is terminated after the completion of phase I without moving to Phase II.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Adverse Events and Dose Limiting Toxicities (Safety and Tolerability) (time frame: 3 months). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03503968, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Feb 2023.

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