NCT03502577

BCMA-Specific CAR T-Cells Combined With a Gamma Secretase Inhibitor (JSMD194) to Treat Relapsed or Persistent Multiple Myeloma

Terminated Phase 1 Last updated 8 January 2024

What this trial tests

Phase 1 trial testing BCMA-specific CAR-expressing T Lymphocytes in Recurrent Plasma Cell Myeloma in 19 participants. Terminated before completion.

Timeline

23 May 2018

Primary endpoint
20 April 2022

20 April 2022

Quick facts

Lead sponsor	Fred Hutchinson Cancer Center
Phase	Phase 1
Status	Terminated
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	19
Start date	23 May 2018
Primary completion	20 April 2022
Estimated completion	20 April 2022
Sites	1 location across United States

Drugs / interventions tested

• BCMA-specific CAR-expressing T Lymphocytes — full drug profile →
• Cyclophosphamide (cyclophosphamide) — full drug profile →
• Fludarabine (FLUDARABINE) — full drug profile →
• Gamma-Secretase Inhibitor LY3039478
• Laboratory Biomarker Analysis — full drug profile →
• Pharmacokinetic Study

Conditions studied

• Recurrent Plasma Cell Myeloma — all drugs for Recurrent Plasma Cell Myeloma →
• Refractory Plasma Cell Myeloma — all drugs for Refractory Plasma Cell Myeloma →

Sponsor

Fred Hutchinson Cancer Center — full company profile →

Who can join

21 and older, any sex, with Recurrent Plasma Cell Myeloma or Refractory Plasma Cell Myeloma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This phase I trial determines the side effects and best dose of B-cell maturation antigen (BCMA)-chimeric antigen receptor (CAR) T-cells when combined with gamma-secretase inhibitor LY3039478 (JSMD194), cyclophosphamide, and fludarabine in treating participants with multiple myeloma that that has come back or remains despite treatment. Placing genes added in the laboratory into immune T-cells may make the T-cells recognize BCMA, a protein on the surface of cancer cells. JSMD194 may enhance the killing of cancer cells by increasing the BCMA expression on multiple myeloma cells, making the targeted BCMA CAR-T treatment more effective. JSMD194 also decreases the amount of BCMA found in the circulation (called soluble BCMA) that is not bound to the myeloma cells. JSMD194 can therefore reduce the potential for soluble BCMA to act as a decoy. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving BCMA CAR T therapy with JSMD194, cyclophosphamide, and fludarabine may work better in treating participants with relapsed or persistent multiple myeloma.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Recent advances and discoveries in the mechanisms and functions of CAR T cells.
   Larson RC, Maus MV. · · 2021 · cited 644× · PMID 33483715 · DOI 10.1038/s41568-020-00323-z
2. γ-Secretase inhibition increases efficacy of BCMA-specific chimeric antigen receptor T cells in multiple myeloma.
   Pont MJ, Hill T, Cole GO, Abbott JJ, et al · · 2019 · cited 251× · PMID 31558469 · DOI 10.1182/blood.2019000050
3. Trial watch: chemotherapy-induced immunogenic cell death in immuno-oncology.
   Vanmeerbeek I, Sprooten J, De Ruysscher D, Tejpar S, et al · · 2020 · cited 179× · PMID 32002302 · DOI 10.1080/2162402x.2019.1703449
4. BCMA-targeted immunotherapy for multiple myeloma.
   Yu B, Jiang T, Liu D. · · 2020 · cited 165× · PMID 32943087 · DOI 10.1186/s13045-020-00962-7
5. Immunotherapy of multiple myeloma.
   Minnie SA, Hill GR. · · 2020 · cited 160× · PMID 32149732 · DOI 10.1172/jci129205
6. Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma.
   Roex G, Timmers M, Wouters K, Campillo-Davo D, et al · · 2020 · cited 137× · PMID 33272302 · DOI 10.1186/s13045-020-01001-1
7. Mechanisms of resistance to chimeric antigen receptor-T cells in haematological malignancies.
   Ruella M, Korell F, Porazzi P, Maus MV. · · 2023 · cited 123× · PMID 37907724 · DOI 10.1038/s41573-023-00807-1
8. Next-Generation CAR T-cell Therapies.
   Young RM, Engel NW, Uslu U, Wellhausen N, et al · · 2022 · cited 123× · PMID 35417527 · DOI 10.1158/2159-8290.cd-21-1683