Clinical trial NCT05739188: Safety and Efficacy of Anti-GPRC5D CAR-T Cells Therapy in the Treatment of r/r MM
Official title: An Investigator-initiated Trial Evaluating the Efficacy and Safety of Anti-GPRC5D CAR-T Cells Therapy in the Treatment of Relapsed / Refractory(r/r) Multiple Myeloma(MM)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma in Relapse
Multiple Myeloma, Refractory
Keywords: CAR-T
GPRC5D
Lead sponsor: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
Sponsor class: OTHER
First posted: 2023-02-22
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: This is a"3+3"dose escalation study, in which three dose groups are set three different dose levels of CAR-T cells:

Dose level one: 3.0×10\^6 /kg±20%; Dose level two:6.0×10\^6 /kg±20%; Dose level three:1.0×10\^7 /kg±20%.
Primary purpose: TREATMENT

Brief summary: It is a single-center, open-labeled, single-arm, non-randomized investigator-initiated trial evaluating the efficacy and safety of anti-GPRC5D CAR-T cells therapy for relapsed and refractory(r/r) multiple myeloma(MM).

Detailed description: This open label, single-arm, Phase I study aims to evaluate the efficacy and safety of Anti-GPRC5D CAR-T in subjects with relapsed and refractory(r/r) multiple myeloma(MM). A leukapheresis procedure will be performed to manufacture Anti-GPRC5D chimeric antigen receptor (CAR) modified T cells. Prior to Anti-GPRC5D CAR-T cells infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. After infusion, the safety and efficacy of CAR-T therapy was evaluated by investigators.

Eligibility criteria: Inclusion Criteria:

1. The patient or his/her guardian understands and voluntarily signs the informed consent, and is expected to complete the follow-up examination and treatment of the study procedure;
2. Age 18-75 years old, gender unlimited;
3. Patients diagnosed with multiple myeloma according to International Myeloma Working Group(IMWG) diagnostic criteria;
4. Subjects who had failed treatment with at least 3 drugs of different mechanisms (including chemotherapy, proteasome inhibitors, immunomodulators, etc.), or had progressed or relapsed during the last treatment period or within 6 months after the end of treatment;
5. The presence of measurable lesions at screening was determined according to any of the following criteria, defined as: (1) serum monoclonal immunoglobulin (M-protein) level ≥1.0 g/dL; (2) urine M protein level ≥200 mg/ 24h; (3) Light chain multiple myeloma diagnosed with no measurable lesion in serum or urine: serum immunoglobulin free light chain ≥10 mg/dL and serum immunoglobulin κ/γ free light chain ratio abnormal;
6. The patient has recovered from the toxicity of the prior treatment, i.e., CTCAE toxicity grade \< 2 (unless the abnormality is related to the tumor or is stable as judged by the investigator and has little impact on safety or efficacy);
7. Eastern cooperative oncology group (ECOG) score is 0-2;
8. Survival is expected to be greater than 3 months;
9. Adequate liver , kidney and cardiopulmonary function;
10. Willingness to complete the informed consent process and to comply with study procedures and visit schedule.

Exclusion Criteria:

1. Have been diagnosed with or treated for aggressive malignancies other than multiple myeloma;
2. Prior antitumor therapy (prior to blood collection for CAR-T preparation) : targeted therapy, epigenetic therapy, or investigational drug therapy within 14 days or at least 5 half-lives, whichever is shorter;
3. It is suspected that MM has involved the central nervous system or meninges and has been confirmed by MRI or CT, or there are other active central nervous system diseases;
4. Clinically significant central nervous system diseases, such as epilepsy, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, psychosis, active central nervous system involvement or cancerous meningitis;
5. HBsAg or HBcAb are positive, and the quantitative detection of hepatitis B virus(HBV) DNA in peripheral blood is more than 100 copies / L;hepatitis C virus (HCV) antibody and HCV RNA in peripheral blood are positive; HIV antibody positive; Syphilis antibody is positive in the first screening;
6. Pregnant or breastfeeding;
7. Severe active viral, bacterial or uncontrolled systemic fungal infections; Hereditary bleeding / coagulation diseases, history of non traumatic bleeding or thromboembolism, other diseases that may increase the risk of bleeding, etc;Patients who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks before screening, or who plan to undergo ASCT during the study period;
8. Any unstable systemic disease: including but not limited to unstable angina, cerebrovascular accident or transient cerebral ischemia (within 6 months before screening), myocardial infarction (within 6 months before screening), congestive heart failure \[New York Heart Association (NYHA) classification ≥ grade III\], severe arrhythmia with poor drug control, liver, kidney or metabolic diseases;
9. Had hypersensitivity or intolerance to any drug used in this study;
10. Persons with serious mental illness;
11. Alcoholics or persons with a history of drug abuse;
12. Systemic diseases judged by researchers to be unstable: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment;
13. Patients with acute/chronic graft-versus-host disease (GVHD) or requiring immunosuppressive therapy for GVHD within 6 months prior to screening;
14. Any unsuitable to participate in this trial judged by the investigator.

Primary outcomes:
measure: Incidence of adverse events(AE) after infusion
timeFrame: Up to 12 months after infusion
measure: Dose limited toxicity (DLT)
timeFrame: Up to 1 month after infusion
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Up to 2 years after infusion
measure: Concentration of CAR-T cells
timeFrame: Days 4, 7, 10, 14 and months 2, 3, 6, 9, 12 after infusion
measure: Progression-free survival(PFS)
timeFrame: Up to 2 years
measure: Overall survival(OS)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Kunming
country: China
facility: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
state: Yunnan
city: Kunming
country: China
facility: No.212 Daguan Road, Xishan District
state: Yunnan
Study officials:
affiliation: 920th Hospital of Joint Logistics Support Force of People's Liberation Army of China
name: Sanbin Wang, MD
role: PRINCIPAL_INVESTIGATOR
References: