APRIL CAR-T Cell Therapy for Patients With BCMA/TACI Positive Relapsed and/or Refractory Multiple Myeloma

Study Overview
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Brief Summary
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A study of APRIL CAR-T cells therapy for patients with BCMA/TACI positive relapsed and/or refractory multiple myeloma

Detailed Description
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This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory BCMA/TACI positive relapsed and/or refractory multiple myeloma. The selections of dose levels and the number of subjects are based on clinical trials of similar foreign products. 36 patients will be enrolled. 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 APRIL CAR-T Cells Therapy for Patients With BCMA/TACI Positive Relapsed and/or Refractory Multiple Myeloma

Conditions
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Multiple Myeloma in Relapse, Multiple Myeloma, Refractory

Intervention / Treatment
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* Drug: APRIL CAR-T cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed diagnosis of BCMA/TACI+ multiple myeloma (MM)： Patients with MM relapsed after BCMA CAR-T therapy; Or MM with positive BCMA/TACI expression; 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. Male or female aged 18-75 years; Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L; Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%; No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%; Estimated survival time ≥ 3 months; ECOG performance status 0 to 2; Patients or their legal guardians volunteer to participate in the studyand sign the 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: 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 APRIL CAR T-cells<br>Each subject receive APRIL CAR T-cells by intravenous infusion | Drug: APRIL CAR-T cells<br>* Each subject receive APRIL CAR T-cells by intravenous infusion<br>* Other names: APRIL 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 APRIL targeted CAR T-cells infusion | 
| Incidence of treatment-emergent adverse events (TEAEs) | Incidence of treatment-emergent adverse events [Safety and Tolerability] | Time Frame: Up to 2 years after APRIL targeted CAR T-cells infusion | 

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) at Month 1, 3, 6, 12, 18 and 24 | At Month 1, 3, 6, 12, 18 and 24 | 
| MM, Overall survival (OS) | From the first infusion of APRIL CAR-T cells to death or the last visit | Up to 2 years after APRIL CAR-T cells infusion | 
| MM, Event-free survival (EFS) | From the first infusion of APRIL CAR-T cells to the occurrence of any event, including death, relapse or gene relapse, disease progression (any one occurs first), and the last visit | Up to 2 years after APRIL CAR-T cells infusion | 
| Quality of life including sports activity | 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 | 
| 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 | 
| 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 | 
| Hospital Anxiety and Depression Scale (HADS) score | Assessment using Hospital Anxiety and Depression Scale (HADS) [max score: 42, min score: 0, higher scores mean a worse outcome] 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/TACI positive