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

Early Phase 1

Recruiting

• Conditions: Multiple Myeloma in Relapse; Multiple Myeloma, Refractory
• Interventions: Drug: APRIL CAR-T cells

• Registration Number: NCT04657861
• Lead Sponsor: Zhejiang University

Brief Summary

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

Detailed Description

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.

Study Timeline

• Study First Submitted: 2020-10-22
• Study First Submitted QC: 2020-12-05
• Study First Posted: 2020-12-08
• Status Verified: 2022-03
• Study Start: 2022-05-03
• Last Update Submitted: 2022-05-03
• Last Update Posted: 2022-05-09
• Primary Completion: 2024-08-20
• Study Completion: 2027-08-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

1. Histologically confirmed diagnosis of BCMA/TACI+ multiple myeloma (MM)：

   1. Patients with MM relapsed after BCMA CAR-T therapy; Or MM with positive BCMA/TACI expression;
   2. Relapsed after hematopoietic stem cell transplantation;
   3. Cases with recurrent positive minimal residual disease;
   4. Extramedullary leision which is hard to be eradicated by chemotherapy or radiotherapy.

2. Male or female aged 18-75 years;

3. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;

4. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥50%;

5. No active infection in the lungs, blood oxygen saturation in indoorair is ≥ 92%;

6. Estimated survival time ≥ 3 months;

7. ECOG performance status 0 to 2;

8. 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:

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 severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
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. Previously treated with any CAR-T cell product or other genetically modified T cell therapies;
8. Creatinine>2.5mg/dl, or ALT / AST > 3 times of normal amounts, or bilirubin>2.0 mg/dl;
9. Other uncontrolled diseases that were not suitable for this trial;
10. Patients with HIV infection;
11. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Administration of APRIL CAR T-cells	APRIL CAR-T cells	Each subject receive APRIL CAR T-cells by intravenous infusion

Primary Outcome Measures

Name	Time	Method
Dose-limiting toxicity (DLT)	Baseline up to 28 days after APRIL targeted CAR T-cells infusion	Adverse events assessed according to NCI-CTCAE v5.0 criteria
Incidence of treatment-emergent adverse events (TEAEs)	Time Frame: Up to 2 years after APRIL targeted CAR T-cells infusion	Incidence of treatment-emergent adverse events \[Safety and Tolerability\]

Secondary Outcome Measures

Name	Time	Method
Multiple Myeloma (MM), Overall response rate (ORR)	At Month 1, 3, 6, 12, 18 and 24	Assessment of ORR (ORR = sCR+CR+VGPR+PR+MR) at Month 1, 3, 6, 12, 18 and 24
MM, Overall survival (OS)	Up to 2 years after APRIL CAR-T cells infusion	From the first infusion of APRIL CAR-T cells to death or the last visit
MM, Event-free survival (EFS)	Up to 2 years after APRIL CAR-T cells infusion	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
Quality of life including sports activity	At Baseline, Month 1, 3, 6, 9 and 12	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
Activities of Daily Living (ADL) score	At Baseline, Month 1, 3, 6, 9 and 12	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
Instrumental Activities of Daily Living (IADL) score	At Baseline, Month 1, 3, 6, 9 and 12	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
Hospital Anxiety and Depression Scale (HADS) score	At Baseline, Month 1, 3, 6, 9 and 12	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

Trial Locations

Locations (1)

The First Affiliated Hospital，College of Medicine, Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China