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

Multiple Myeloma Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03915184
• Other study ID #: CT053-MM-02 (LUMMICAR STUDY 2)
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: September 25, 2019
• Est. completion date: December 31, 2034

Study information

• Verified date: December 2023
• Source: CARsgen Therapeutics Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 105
• Est. completion date: December 31, 2034
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Biological:
• zevor-cel
A single autologous chimeric antigen receptor-B-cell maturation antigen (CAR-BCMA T cell) infusion

Locations

Country	Name	City	State
Canada	Princess Margaret Hospital	Toronto	Ontario
United States	Dana Farber Cancer Center	Boston	Massachusetts
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Colorado Blood Cancer Institute	Denver	Colorado
United States	MD Anderson	Houston	Texas
United States	Methodist Hosptial	Houston	Texas
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	TriStar CMC	Nashville	Tennessee
United States	Mayo Clinic Hospital	Phoenix	Arizona
United States	Mayo	Rochester	Minnesota
United States	Huntsman Cancer Center	Salt Lake City	Utah
United States	UCSF	San Francisco	California
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
CARsgen Therapeutics Co., Ltd.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	BCMA bone marrow expression and soluble BCMA expression in blood	Myeloma cell BCMA expression and serum soluble BCMA	Day 1 - Month 60
Other	Cytokine profiling	cytokine levels (such as IL-6, INF, et al)	Day 1 - Month 60
Other	zevor-cel product profiling vs clinical safety and efficacy	zevor-cel product characteristics	Day 1 - Month 60
Primary	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
Primary	Identification of Maximum Tolerated Dose (MTD)	Incidence of dose-limiting toxicities (DLTs)	Day 1 - Month 60
Primary	Objective response rate	Objective response rate (ORR) per IMWG by IRC read	Day 1 - Month 60
Secondary	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
Secondary	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
Secondary	Evaluate zevor-cel PK profile	CAR transgene copy number, peak value, AUC, in vivo persistence	Day 1 - Month 60
Secondary	Evaluate ADA profile	Percentage of patients with anti-zevor-cel drug antibodies	Day 1 - Month 60
Secondary	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
Secondary	Evaluate utilization of hospital resources	Duration of hospitalization and ICU	Day 1 - Month 60