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

Detailed Description
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In this study, 100 patients with relapsed refractory multiple myeloma were proposed to undergo BCMA CAR-T cell therapy. Under the premise that its safety has been clarified in previous studies, further observation and evaluation of the effectiveness of BCMA 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 BCMA CAR-T cell treatment for relapsed refractory multiple myeloma were accumulated, including rare and delayed complications.

Official Title
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Clinical Trial for the Safety and Efficacy of 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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* Biological: BCMA Targeted CAR T-cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. 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; Repeated MRD(+) refractory resistant cases Extramedullary leision which is hard to be eradicated by chemotherapy or radiotherapy. 2. Anticipated survival time more than 12 weeks; 3. Transplant patients, regardless of their previous treatment, are eligible after relapse; 4. 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; With a graft-versus-host response, immunosuppressants are required; 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.
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. | Biological: 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