A Study of DeepTag-GPRC5D Targeted CAR-T Cells Therapy for Refractory/Relapsed Multiple Myeloma

Study Overview
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Brief Summary
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Clinical Trial for the safety and efficacy of DeepTag-GPRC5D targeted CAR-T cells therapy for refractory/relapsed multiple myeloma

Detailed Description
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In this study, 60 patients with relapsed refractory multiple myeloma were proposed to undergo DeepTag-GPRC5D CAR-T cell therapy. Under the premise that its safety has been clarified in previous studies, further observation and evaluation of the effectiveness of DeepTag-GPRC5D CAR-T cell therapy for relapsed refractory multiple myeloma; At the same time, on the basis of expanding the sample size, more safety data on DeepTag-GPRC5D CAR-T cell treatment for relapsed refractory multiple myeloma were accumulated, including rare and delayed complications.

Official Title
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A Study of DeepTag-GPRC5D Targeted CAR-T Cells Therapy for Refractory/Relapsed Multiple Myeloma

Conditions
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Relapse/Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: DeepTag-GPRC5D Targeted CAR T-cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Those who voluntarily participated in this trial and provided informed consent; 2. Gender unlimited，18<Age≤75; 3. Estimated life expectancy of minimum of 12 weeks; 4. ECOG 0-2; 5. Diagnosed as multiple myeloma according to the IMWG criteria; 6. Subjects failed treatment with at least 3 prior lines of therapy (including chemotherapy based on proteasome inhibitors (PIs) ，immunomodulatory agents (IMiDs) and CD38 antibody）, or recived the above three treatment methods experienced disease progression or recurrence during the most recent treatment process or within 6 months after the end of treatment, Difficulty in treatment includes primary difficulty in treatment ( patient has not achieved minimal remission or disease progression during treatment) or secondary difficulty in treatment (patient develops disease progression within 60 days after completion of treatment); 7. Women have a negative urine pregnancy test before the start of medication administration and agree to take effective contraceptive measures during the trial period until the last follow-up; 8. The blood routine meets the following standards: Lymphocyte count>0.3×10e9/L; Neutrophils ≥0.5×10e9/L; Hemoglobin ≥60g/L; Platelet ≥30×10e9/L Exclusion Criteria: 1. History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases; 2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; 3. Pregnant (or lactating) women; 4. Patients with HIV infection; 5. Active infection of hepatitis B virus or hepatitis C virus; 6. Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids; 7. The proiferation rate is less than 5 times response to CD3/CD28 co-stimulation signal; 8. Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl; 9. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study; 10. Patients who received anti-cancer chemotherapy or other medications within 2 weeks before screening; 11. Uncontrolled malignant tumors except MM, excluding malignant tumors that received radical treatment and no active disease was found within 3 years before enrollment; 12. Patients who received autologous hematopoietic stem cell transplantation (ASCT) within 8 weeks before screening, or who plan to undergo ASCT during the study period; 13. Patients received allogeneic stem cell therapy; 14. Any unsuitable to participate in this trial judged by the investigator.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Administration of DeepTag-GPRC5D Targeted CAR T-cells<br>Dose escalation follows the standard 3+3 dose escalation design. A total of 3 dose levels are set for subjects. | Biological: DeepTag-GPRC5D Targeted CAR T-cells<br>* Each subject receive DeepTag-GPRC5DTargeted CAR T-cells by intravenous infusion<br>* Other names: DeepTag-GPRC5D Targeted CAR T-cells injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity (DLT) | Adverse events assessed according to NCI-CTCAE v5.0 criteria | Up to 28 years after Treatment | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 2 years after Treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Myeloma (MM), Overall response rate (ORR) | Assessment of ORR (ORR = sCR+CR+VGPR+PR+MR) | Up to 2 years after Treatment | 
| Progression-free survival (PFS) | The time from randomization or start of study treatment until objective tumor progression or death | Up to 2 years after Treatment | 
| Duration of remission,DOR | The time from CR/CRi and PR to disease relapsed or death due to disease | Up to 1 years after Treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Myeloma, DeepTag-GPRC5D CAR T-cell