Clinical trial NCT05838131: Study of CT071 Injection in RRMM or PPCL
Official title: A Clinical Trial to Explore the Safety and Efficacy of CT071 Injection in Patients With Relapsed/Refractory Multiple Myeloma or Primary Plasma Cell Leukemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Multiple Myeloma
Primary Plasma Cell Leukemia
Keywords: multiple myeloma
primary plasma cell leukemia
CAR-T
Lead sponsor: Shanghai Changzheng Hospital
Sponsor class: OTHER
Collaborators: name: CARsgen Therapeutics Co., Ltd.
First posted: 2023-05-01
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: A Clinical Trial to Explore the Safety and Efficacy of CT071 injection in Patients with Relapsed/Refractory Multiple Myeloma or Primary Plasma Cell Leukemia

Detailed description: This trial is a single-arm, open-label, dose-finding, first-in-human clinical trial. The main aim of this study is to preliminarily evaluate the safety and tolerability of CT071 after infusion, and explore the dose range of CT071 in patients with relapsed/refractory multiple myeloma or primary plasma cell leukemia, so as to determine the possible recommended therapeutic dose (RD).

Eligibility criteria: Inclusion Criteria:

1. Volunteer to participate in the clinical trial; fully understand and are informed of this trial and sign the informed consent form; Willing to follow and able to complete all trial procedures;
2. Age ≥ 18 years, male or female;
3. Patients with multiple myeloma who have received at least three lines therapy for multiple myeloma (requires relapse, progression, non-response after treatment with at least 1 proteasome inhibitor and at least 1 immunomodulator.
4. Patients with primary plasma cell leukemia progressed after treatment with at least 1 regimen;
5. Progressive disease at the time of enrollment according to the IMWG consensus for myeloma or plasma cell leukemia;
6. Have any of the following evaluable conditions:

   1. Serum M-protein ≥ 5 g/L;
   2. 24-hour urine M-protein ≥ 200 mg;
   3. Abnormal serum free light chain (sFLC) ratio and affected FLC ≥ 100 mg/L in subjects with multiple myeloma who did not meet evaluable criteria for either serum or urine M-protein levels;
   4. Circulating plasma cells ≥ 5% (PCL subjects only);
7. Estimated survival \> 12 weeks;
8. Eastern Cooperative Oncology Group (ECOG) score 0-2;
9. Subjects had adequate organ function.
10. Female subjects of childbearing potential must have a negative serum pregnancy test at screening, be willing to use a highly effective and reliable method of contraception within 1 year after receiving the trial treatment, and absolutely prohibit egg donation during the trial and within 1 year after receiving the trial treatment;
11. Male subjects, if sexually active with a female of childbearing potential, are willing to use a highly effective and reliable method of contraception for 1 year after receiving trial treatment. All male subjects are absolutely prohibited from donating sperm during the trial and for 1 year after receiving the trial treatment.

Exclusion Criteria:

1. Pregnant or lactating females;
2. Patients with a history of neurological disease, such as epilepsy, intracranial hemorrhage, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disease, memory impairment, spinal cord compression, psychiatric disease or any disease involving the central nervous system, or suspected central nervous system (CNS) metastasis;
3. Patients with other incurable malignant tumors within 5 years or at the same time, except for those with very low degree of malignancy;
4. Patients with active autoimmune diseases, including but not limited to psoriasis, rheumatoid arthritis, inflammatory bowel disease and other patients requiring long-term immunosuppressive therapy;
5. Received allogeneic stem cell transplantation within two years prior to screening;
6. Received autologous stem cell transplantation within 12 weeks prior to screening, or plan to receive autologous stem cell transplantation during the trial;
7. Any uncontrolled disease or disorder with important clinical significance investigator considered not applicable for the study;
8. Patients who had any uncontrolled active infection (defined as the presence of persistent signs or symptoms associated with infection that did not improve despite appropriate antiinfective treatment) or who required intravenous antiinfective agents (except for prophylactic treatment) within 4 weeks before apheresis. If there is clinical indications, investigators should consider screening EBV, CMV, and other related pathogenic microorganisms;
9. Major surgery within 2 weeks prior to screening, or planning to undergo major surgery within 4 weeks after trial treatment (excluding cataract and other surgery under local anesthesia);
10. Received treatment for the disease under study within 2 weeks prior to apheresis(or within five half-lives of the drug, whichever is shorter), including but not limited to cytotoxic therapy, proteasome inhibitors, immunomodulators, targeted therapy, radiotherapy, epigenetic therapy, etc.; Received anti-PD-1/PD-L1 monoclonal antibody or other investigational drug/invasive medical device within 4 weeksprior to apheresis;
11. Vaccination with live attenuated vaccine or mRNA vaccine within 8 weeks and inactivated vaccine within 4 weeks before screening;
12. Patients who are allergic or intolerant to CLD drugs, tocilizumab, or allergic to the ingredients of CT071 cell infusion preparation (DMSO); Or previous history of other severe allergies, such as anaphylactic shock;
13. Positive test results for any of the following: human immunodeficiency virus (HIV) antibody, Treponema pallidum antibody, hepatitis C virus (HCV) RNA, hepatitis B virus (HBV) surface antigen (HBsAg), HBV DNA;
14. The toxicities caused by the previous treatment have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) ≤ Grade 1, except for alopecia and other tolerable events as judged by the investigator;
15. Left ventricular ejection fraction (LVEF) \< 50%;
16. Oxygen saturation \< 92% at room air;
17. Received glucocorticoids within 7 days prior to apheresis, with the exception of inhaled glucocorticoids and physiologic replacement doses;
18. Other conditions considered inappropriate for participation in this clinical trial by the investigator.

Primary outcomes:
measure: DLT after CT071 infusion
timeFrame: Assessed from the date of first dose of study treatment until 21~28 days
measure: AE of Neurotoxicity and cytokine release syndrome after CT071 infusion
timeFrame: From first dose of study drug adminisration to end of treatment (up to 12 months)
measure: Adverse Events (AE) after CT071 infusion
timeFrame: From first dose of study drug administration to end of treatment (up to 12 months)
Secondary outcomes:
measure: Level of CAR-T Cell Expansion (proliferation), and Persistence
timeFrame: From first dose of study drug administration to 26 weeks
measure: Cytokines in the peripheral blood after CT071 infusion
timeFrame: From first dose of study drug administration to 4 weeks
measure: Preliminary evaluation of immunogenicity
timeFrame: From first dose of study drug administration to end of treatment (up to 12 months)
measure: Overall response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria after CT071 infusion
timeFrame: From first dose of study drug administration to end of treatment (up to 12 months)
measure: Rate of very good partial response (VGPR) and above, complete response/stringent complete response (CR/sCR);
timeFrame: From first dose of study drug administration to end of treatment (up to 12 months)
measure: Duration of response (DOR)
timeFrame: From first dose of study drug administration to end of treatment (up to 12 months)
measure: Minimal residual disease (MRD) negative rate;
timeFrame: From first dose of study drug administration to end of treatment (up to 12 months)
measure: Time to response (TTR)
timeFrame: From first dose of study drug administration to end of treatment (up to 12 months)
measure: Progression-free survival (PFS)
timeFrame: From first dose of study drug administration to end of treatment (up to 12 months)
measure: Overall survival (OS)
timeFrame: From first dose of study drug administration to death
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
Study officials:
affiliation: Shanghai Changzheng Hospital
name: Juan Du
role: PRINCIPAL_INVESTIGATOR
References: