Clinical trial NCT03915184: Clinical Trial to Evaluate Zevor-cel (CT053) in Patients With Relapsed and/or Refractory Multiple Myeloma (LUMMICAR STUDY 2)
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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: CAR-T
Carcinoma
Carcinoma, Multiple Myeloma
CT053
zevor-cel
Lead sponsor: CARsgen Therapeutics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-04-16
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Incidence of Treatment Related adverse events (AEs)
timeFrame: Day 1 - Month 60
measure: Identification of Maximum Tolerated Dose (MTD)
timeFrame: Day 1 - Month 60
measure: Objective response rate
timeFrame: Day 1 - Month 60
Secondary outcomes:
measure: Evaluate additional clinical efficacy outcomes with zevor-cel treatment in patients with rrMM
timeFrame: Day 1 - Month 60
measure: Determine the efficacy of zevor-cel treatment in patients with rrMM, by investigator assessment
timeFrame: Day 1 - Month 60
measure: Evaluate zevor-cel PK profile
timeFrame: Day 1 - Month 60
measure: Evaluate ADA profile
timeFrame: Day 1 - Month 60
measure: Evaluate HRQoL in patients with rrMM from baseline up to study completion
timeFrame: Day 1 - Month 60
measure: Evaluate utilization of hospital resources
timeFrame: Day 1 - Month 60
Other outcomes:
measure: BCMA bone marrow expression and soluble BCMA expression in blood
timeFrame: Day 1 - Month 60
measure: Cytokine profiling
timeFrame: Day 1 - Month 60
measure: zevor-cel product profiling vs clinical safety and efficacy
timeFrame: Day 1 - Month 60
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: San Francisco
country: United States
facility: UCSF
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo
state: Minnesota
city: Nashville
country: United States
facility: TriStar CMC
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Houston
country: United States
facility: Methodist Hosptial
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Center
state: Utah
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
Study officials:
affiliation: Mayo
name: Shaji Kumar, MD
role: PRINCIPAL_INVESTIGATOR
References: