Trial document




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  DRKS00020221

Trial Description

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Title

A Phase I study of MAGE-A1-specific TCR-transduced T cells in patients with relapsed/refractory multiple myeloma

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Trial Acronym

MAGE-A1-TCR

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URL of the Trial

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Brief Summary in Lay Language

T1367 T cells are a new cellular therapy against relapsed/refractory multiple myeloma. White blood cells of the patient (T cells) will be filtered from the blood and genetically modified to express a new receptor. That receptor enables them to detect and kill cancer cells expressing the protein “MAGE-A1”. T cells will be given back to the patient by intravenous injection following a short course of chemotherapy. Escalating doses of the therapeutic drug will be administered to 4 groups including 3-6 patients each. This trial intends to evaluate the safety and tolerability of this new cellular therapy and will monitor its efficacy against multiple myeloma.

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Brief Summary in Scientific Language

This is a phase I, single-center, single-arm, open-label, dose escalation trial in patients with relapsed/refractory multiple myeloma. The study comprises four cohorts with 3-6 patients each (3+3 design) treated with ascending doses of the IMP T1367 T cells. T1367 T cells are autologous patient-derived CD8+ T cells, engineered through retroviral transduction to express the MAGE-A1 specific TCR T1367. This redirects the T cells to recognize the MAGE-A1 derived nonamer epitope MAGE-A1(278-286) presented by HLA-A*02:01 on the surface of myeloma cells.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00020221
  •   2020/01/06
  •   [---]*
  •   yes
  •   Approved
  •   17/0259, Ethik-Kommission des Landes Berlin
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Secondary IDs

  •   2017-001208-30 
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Health Condition or Problem studied

  •   C90.0 -  Multiple myeloma
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Interventions/Observational Groups

  •   T1367 T Cells
    Cyclophosphamid 300 mg / m² for 3 days
    Fludarabin 30 mg / m² for 3 days
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I
  •   No
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Primary Outcome

To evaluate the safety and tolerability of single escalating doses of autologous T cells modified to express the MAGE-A1-specific TCR T1367 for patients with relapsed/refractory Multiple Myeloma

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Secondary Outcome

To characterize T1367 T cells with respect to their in vivo expansion and persistence.
To evaluate the impact of T1367 T cells on disease activity.
To evaluate the impact of T1367 T cells on survival.

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
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Recruitment

  •   Planned
  •   2020/01/05
  •   12
  •   Monocenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

1. A diagnosis of relapsed and/or refractory MM requiring systemic therapy.
2. At least three prior therapy lines including proteasome inhibitors, alkylating drugs, immunomodulatory drugs and antibodies alone or in combination. Induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen.
3. Expression of MAGE-A1 on more or equal than 30 % of myeloma cells by immunohistochemistry in a bone marrow biopsy or biopsy of extramedullary manifestation. The analysis of archival material not older than six months is permitted for MAGE-A1 testing unless a systemic treatment for MM has been administered after biopsy (except Corticosteroids).
4. Minimal life expectancy of 3 months.
5. HLA-A*02:01 genotype.
6. Age ≥18 years
7. Agree to use safe contraception
8. At least 14 days from prior therapy line at leukapheresis
9. ECOG performance status 0-2
10. Adequate cardiopulmonary, renal and hepatic function
a. No dyspnea at rest
b. ALT, AST ≤ 3 x ULN
c. LVEF ≥ 35 %
d. Creatinine clearance ≥30 ml/min according to Cockcroft and Gault equation
e. Total bilirubin ≤ 1.5 x ULN except in case of Gilbert’s disease
11. Ability to understand and sign the Informed Consent Form

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Exclusion Criteria

1. History of allogeneic stem cell transplantation
2. Treatment with any prior gene therapy or gene-modified cellular immunotherapy
3. HIV infection
4. Active or chronic Hepatitis
5. Have any active and uncontrolled infection
6. Known or suspected hypersensitivity or intolerance to the IMP, Cyclophosphamide, Fludarabine, any other excipient and Tocilizumab.
7. Pregnancy or lactation: Females are eligible to participate if not pregnant and not breastfeeding.
8. Inadequate venous access for or contraindications to leukapheresis.
9. Any other condition requiring high-dose corticosteroid treatment in the two weeks prior to leukapheresis.
10. Juvenile rheumatoid arthritis, active rheumatoid arthritis or other active inflammatory joint diseases.
11. Subjects who are legally institutionalized, or subjects under judicial protection
12. Subjects with an immediate family member (i.e., spouse, parent/legal guardian, sibling or a child) being a member of study site staff or being a member of the sponsor’s study team.
13. Participation in another clinical trial, except for observational studies

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Addresses

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    • Charité Campus Berlin Buch
    • Mr.  Professor  Thomas  Blankenstein 
    • Lindenberger Weg 80
    • 13125  Berlin
    • Germany
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    • Charité Campus Berlin Buch
    • Mr.  Professor  Thomas  Blankenstein 
    • Lindenberger Weg 80
    • 13125  Berlin
    • Germany
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    • Charité Campus Benjamin Franklin
    • Mr.  Matthias  Obenaus 
    • Hindenburgdamm 30
    • 12203  Berlin
    • Germany
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Sources of Monetary or Material Support

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    • Bundesministerium für Bildung und Forschung Dienstsitz Bonn
    • Heinemannstr. 2
    • 53175  Bonn
    • Germany
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

  •   Ethikvotum
  •   Prüfprotokoll
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* This entry means the parameter is not applicable or has not been set.