Clinical Trial to Evaluate Zevor-cel (CT053) in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 2)

Open Label, Multi-center, Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Autologous CAR BCMA T Cells (CT053) in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 2)

A phase 1b/2, open label, multi-center, Clinical Study of Chimeric Antigen Receptor T Cells targeting BCMA in patients with relapsed and or refractory multiple myeloma.

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: zevor-cel

Detailed Description

This is an open label, multi-center, phase 1b/2 clinical trial to evaluate the safety and efficacy of autologous chimeric antigen receptor-B-cell maturation antigen (CAR-BCMA T cell; zevor-cel/CT053) in patients with relapsed and or refractory multiple myeloma.

Phase 1b of the study will be dose escalation followed by an expansion cohort. After recommended Phase 2 dose is identified in Phase 1b, the enrollment of Phase 2 will start. Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of investigational drug product (zevor-cel). Following manufacture of the drug product, subjects will receive lymphodepletion prior to zevor-cel infusion. All subjects who complete the study, as well as those who withdraw from the study after receiving zevor-cel for reasons other than death or meeting the early termination criteria, will be asked to continue to undergo a 15-year long-term follow-up study.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, MSG 2C4
      • Princess Margaret Hospital
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Hospital
  • California
    • San Francisco, California, United States, 94143
      • UCSF
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Florida
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • TriStar CMC
  • Texas
    • Dallas, Texas, United States, 76021
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • MD Anderson
    • Houston, Texas, United States, 77030
      • Methodist Hosptial
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Huntsman Cancer Center
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily signed consent;
2. Age of ≥ 18 and < 80 years;
3. Received sufficient prior lines of myeloma therapy;
4. Received treatment with at least one proteasome inhibitor, one IMiD and CD38 anti body.
5. The patient must be refractory to the last line of therapy.
6. The patients should have measurable disease per IMWG definition.
7. Estimated life expectancy > 12 weeks;
8. ECOG performance score 0-1;
9. Patients should have reasonable CBC counts, renal and hepatic functions;
10. Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis;
11. Women of childbearing age must undergo a serum pregnancy test with negative results before screening, and are willing to use effective and reliable method of contraception for at least 12 months after T cell infusion;
12. Men must be willing to use effective and reliable method of contraception for at least 12 months after T cell infusion.

Exclusion Criteria:

1. Pregnant or lactating women;
2. HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infection;
3. Any uncontrolled active infection;
4. AEs from previous treatment that have not recovered;
5. Patients who have had anti-BCMA therapy;
6. Patients who have graft versus host disease (GvHD);
7. Patients have received stem cell transplantation one year before leukapheresis;
8. Patients have received any anti-cancer treatment before leukapheresis;
9. Patients have received steroids before leukapheresis or lymphodepletion;
10. Patients have plasma cell leukemia, Waldenström macroglobulinemia, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome or clinically significant symptomatic immunoglobulin light chain (AL) amyloidosis with evidence of end-organ damage;
11. Patients have been administered live attenuated vaccine before leukapheresis or lymphodepletion;
12. Patients allergic to Flu, Cy, tocilizumab, dimethyl sulfoxide (DMSO) or zevor-cel CAR BCMA T cell;
13. Patients have clinical significant cardiac conditions that researchers believe that participating in this clinical trial may endanger the health of the patients;
14. Patients have clinical significant pulmonary conditions;
15. Patients are known to have active autoimmune diseases including but not limited to psoriasis, rheumatoid arthritis and other needs of long-term immunosuppressive therapy;
16. Patients with second malignancies in addition to MM are not eligible;
17. Patients have central nervous system (CNS) metastases or CNS involvement;
18. Patients have significant neurologic disorders;
19. Patients are unable or unwilling to comply with the requirements of clinical trial;
20. Patients have received major surgery prior to leukapheresis or prior to lymphodepletion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CAR-BCMA T Cells; Phase 1b will include a dose escalation followed by an expansion cohort to determine the recommended dose for the expansion part. After recommended Phase 2 is determined, patients in Phase 2 will be treated.	Biological: zevor-cel; A single autologous chimeric antigen receptor-B-cell maturation antigen (CAR-BCMA T cell) infusion; Other Names: CAR-BCMA T Cell Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment Related adverse events (AEs)	Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs)	Day 1 - Month 60
Identification of Maximum Tolerated Dose (MTD)	Incidence of dose-limiting toxicities (DLTs)	Day 1 - Month 60
Objective response rate	Objective response rate (ORR) per IMWG by IRC read	Day 1 - Month 60

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate additional clinical efficacy outcomes with zevor-cel treatment in patients with rrMM	Disease-specific response criteria including, but not limited to: complete response (CR), MRD, very good partial response (VGPR), and partial response (PR) according to the International Myeloma Working Group (IMWG) Uniform Response Criteria for Multiple Myeloma, Time to Response, Time to Progression, Progression Free Survival, best response and Overall Survival	Day 1 - Month 60
Determine the efficacy of zevor-cel treatment in patients with rrMM, by investigator assessment	ORR, DOR, FPS, OS, MRD, time to response, time to progression, best tumor response	Day 1 - Month 60
Evaluate zevor-cel PK profile	CAR transgene copy number, peak value, AUC, in vivo persistence	Day 1 - Month 60
Evaluate ADA profile	Percentage of patients with anti-zevor-cel drug antibodies	Day 1 - Month 60
Evaluate HRQoL in patients with rrMM from baseline up to study completion	Change from baseline in HRQoL as measured by EORTC QLQ-C30 and QLQ-MY20	Day 1 - Month 60
Evaluate utilization of hospital resources	Duration of hospitalization and ICU	Day 1 - Month 60

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
BCMA bone marrow expression and soluble BCMA expression in blood	Myeloma cell BCMA expression and serum soluble BCMA	Day 1 - Month 60
Cytokine profiling	cytokine levels (such as IL-6, INF, et al)	Day 1 - Month 60
zevor-cel product profiling vs clinical safety and efficacy	zevor-cel product characteristics	Day 1 - Month 60

Collaborators and Investigators

• Sponsor: CARsgen Therapeutics Co., Ltd.
• Investigators: Principal Investigator: Shaji Kumar, MD, Mayo

Study record dates

Study Major Dates

• Study Start (Actual): September 25, 2019
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2034

Study Registration Dates

• First Submitted: April 3, 2019
• First Submitted That Met QC Criteria: April 12, 2019
• First Posted (Actual): April 16, 2019

Study Record Updates

• Last Update Posted (Actual): December 19, 2023
• Last Update Submitted That Met QC Criteria: December 18, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Carcinoma; CAR-T; Carcinoma, Multiple Myeloma; CT053; zevor-cel
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CT053-MM-02 (LUMMICAR STUDY 2)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No