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

Multiple Myeloma in Relapse Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04657861
• Other study ID #: APRIL-001
• Status: Recruiting
• Phase: Early Phase 1
• Start date: May 3, 2022
• Est. completion date: August 20, 2027

Study information

• Verified date: March 2022
• Source: Zhejiang University
• Contact: He Huang, PhD
• Phone: 86-13605714822
• Email: hehuangyu[@]126.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 36
• Est. completion date: August 20, 2027
• Est. primary completion date: August 20, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Multiple Myeloma in Relapse
• Multiple Myeloma, Refractory
• Neoplasms, Plasma Cell

Intervention

Drug:
• APRIL CAR-T cells
Each subject receive APRIL CAR T-cells by intravenous infusion

Locations

Country	Name	City	State
China	The First Affiliated Hospital,College of Medicine, Zhejiang University	Hangzhou	Zhejiang

Sponsors (2)

Lead Sponsor	Collaborator
Zhejiang University	Yake Biotechnology Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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