A Study of Humanized BCMA-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 humanized BCMA-targeted CAR-T cells therapy for refractory/relapsed multiple myeloma

Detailed Description
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This is a single arm, open-label, single-center study. This study is indicated for relapsed BCMA+ multiple myeloma, the selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 50 patients will be enrolled for this trial. Primary objective is to explore the safety, main consideration is dose-related safety.

Official Title
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Clinical Trial for the Safety and Efficacy of Humanized BCMA-targeted CAR-T Cells Therapy for Refractory/Relapsed Multiple Myeloma

Conditions
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Relapse Multiple Myeloma, Refractory Multiple Myeloma

Intervention / Treatment
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* Drug: BCMA Targeted CAR T-cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of multiple myeloma (MM): Patients with BCMA positive relapsed/refractory MM; Relapsed after hematopoietic stem cell transplantation; Cases with recurrent positive minimal residual disease; Extramedullary leision which is hard to be eradicated by chemotherapy or radiotherapy. Anticipated survival time more than 12 weeks; Male or female aged 30-75 years; Those who voluntarily participated in this trial and provided informed consent. Exclusion Criteria: Subjects with any of the following exclusion criteria were not eligible for this trial: History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases; Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past; Pregnant (or lactating) women; Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis); Active infection of hepatitis B virus or hepatitis C virus; Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids; Previously treated with any CAR-T cell product or other genetically-modified T cell therapies; Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl; Other uncontrolled diseases that were not suitable for this trial; Patients with HIV infection; Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.

Ages Eligible for Study
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Minimum Age: 30 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 BCMA 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. | Drug: BCMA Targeted CAR T-cells<br>* Each subject receive BCMA Targeted CAR T-cells by intravenous infusion<br>* Other names: BCMA 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 | Baseline up to 28 days after BCMA targeted CAR T-cells infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Up to 2 years after BCMA targeted CAR T-cells infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate (ORR) | Assessment of ORR at Day 28 | At Day 28 | 
| Overall survival (OS) | Assessment of OS at Month 6, 12, 24 | At Month 6, 12, 24 | 
| Quality of life(EORTC QLQ-C30) Core 30 (EORTC QLQ-C30) | Assessment using European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) scale [For item1-28: max score: 112, min score: 28, higher scores mean a better outcome; for item 28-29: max score: 14, min score: 2, higher scores mean a worse outcome] to measure Quality of life at Baseline, Month 1, 3, 6, 9 and 12 | At Baseline, Month 1, 3, 6, 9 and 12 | 
| Instrumental Activities of Daily Living (IADL) score | Assessment of Instrumental Activities of Daily Living (IADL) scale [max score: 56, min score: 14, higher scores mean a worse outcome] at Baseline, Month 1, 3, 6, 9 and 12 | At Baseline, Month 1, 3, 6, 9 and 12 | 
| Activities of Daily Living (ADL) score | Assessment using Activities of Daily Living (ADL) scale (Barthel Index) [max score: 100, min score: 0, higher scores mean a better outcome] at Baseline, Month 1, 3, 6, 9 and 12 | At Baseline, Month 1, 3, 6, 9 and 12 | 
| Hospital Anxiety and Depression Scale (HADS) score | Assessment of Hospital Anxiety and Depression Scale (HADS) score at Baseline, Month 1, 3, 6, 9 and 12 | At Baseline, Month 1, 3, 6, 9 and 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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multiple myeloma, CAR T-cell therapy, BCMA