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

Phase 1

Recruiting

• Conditions: C90.0; Multiple myeloma

• Registration Number: DRKS00020221
• Lead Sponsor: Charité Campus Berlin Buch

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-06
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 12

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

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

Study & Design

• Study Type: interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
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

Secondary Outcome Measures

Name	Time	Method
To characterize T1367 T cells with respect to their in vivo expansion and persistence.<br>To evaluate the impact of T1367 T cells on disease activity.<br>To evaluate the impact of T1367 T cells on survival.