Clinical trial NCT04657861: APRIL CAR-T Cell Therapy for Patients With BCMA/TACI Positive Relapsed and/or Refractory Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Multiple Myeloma in Relapse
Multiple Myeloma, Refractory
Keywords: Multiple Myeloma
CAR T-cell therapy
BCMA/TACI positive
Lead sponsor: Zhejiang University
Sponsor class: OTHER
Collaborators: name: Yake Biotechnology Ltd.
First posted: 2020-12-08
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Dose-limiting toxicity (DLT)
timeFrame: Baseline up to 28 days after APRIL targeted CAR T-cells infusion
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Time Frame: Up to 2 years after APRIL targeted CAR T-cells infusion
Secondary outcomes:
measure: Multiple Myeloma (MM), Overall response rate (ORR)
timeFrame: At Month 1, 3, 6, 12, 18 and 24
measure: MM, Overall survival (OS)
timeFrame: Up to 2 years after APRIL CAR-T cells infusion
measure: MM, Event-free survival (EFS)
timeFrame: Up to 2 years after APRIL CAR-T cells infusion
measure: Quality of life including sports activity
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Activities of Daily Living (ADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Instrumental Activities of Daily Living (IADL) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
measure: Hospital Anxiety and Depression Scale (HADS) score
timeFrame: At Baseline, Month 1, 3, 6, 9 and 12
Other outcomes:
Locations:
city: Hangzhou
country: China
facility: The First Affiliated Hospital，College of Medicine, Zhejiang University
state: Zhejiang
Study officials:
References: