A Early Phase 1 Clinical Trial to Evaluate the Safety and Efficacy of Human Derived Anti-BCMA CAR-T Injection for Subjects with Relapsed/Refractory Multiple Myeloma

Hrain Biotechnology Co., Ltd.1 site in 1 country18 target enrollmentFebruary 9, 2022

ConditionsMultiple Myeloma

InterventionsHuman Derived anti-BCMA CAR-T Injection

DrugsHuman Derived anti-BCMA CAR-T Injection

Overview

Phase: Early Phase 1
Intervention: Human Derived anti-BCMA CAR-T Injection
Conditions: Multiple Myeloma
Sponsor: Hrain Biotechnology Co., Ltd.
Enrollment: 18
Locations: 1
Primary Endpoint: Dose limited toxicity(DLT)
Status: Active, not recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This study is a single-arm, open-label, dose-escalation trial to explore the safety, tolerability and pharmacokinetic/pharmacodynamics characteristics of Human Derived anti-BCMA CAR-T Injection , and to preliminarily observe the efficacy of the trial drug in patients with relapsed/refractory multiple myeloma.

Detailed Description

Subjects withe relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility including disease assessments, a physical exam, Electrocardiograph, Computed tomography（CT）/Magnetic Resonance Imaging(MRI)/Positron Emission Tomography（PET）,liver/renal function tests, complete blood count with differential and complete metabolic profile and etc.. Subjects will receive precondtioning chemotherapy prior to the infusion of BCMA CAR- T cells. After the infusion, subjects will be followed for adverse events pharmacokinetic/pharmacodynamics characteristics, efficacy, of BCMA CAR-T cells. Study procedures may be performed while hospitalized.

Registry

clinicaltrials.gov

Start Date

February 9, 2022

End Date

December 31, 2025

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Hrain Biotechnology Co., Ltd.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Subjects must meet all of the following criteria to be enrolled:
•Subjects volunteer to participate in clinical trails, understand and inform the trials and sign informed consent form, be willing to complete all the trial procedures;
•18 to 75 years old (including cut-off value), Male and female;
•Expected survival \> 12 weeks;
•Previously diagnosed as multiple myeloma by IMWG updated criteria (2014);
•One of the following indicators is satisfied:
•Serum M protein: for immunoglobulin G (IgG) type , M protein≥ 10 g/L, or for immunoglobulin A (IgA) type , M protein \> 5g/L, or for immunoglobulin D (IgD) type , M protein, IgD exceeds upper limit of normal range.
•Urine M protein ≥ 200 mg/24h;
•Serum free light chain ≥ 100 mg/L and Serum free light chain ratio is abnormal ;
•Patients with relapsed/refractory multiple myeloma. Relapsed is defined as: Patients have disease progression after at least three-line treatment regimens. Patients previously received at least 3 different mechanisms treatment regimens for multiple myeloma, including protease inhibitors and immunomodulators; Refractory is defined as: Patients who achieved minimal response(MR) or above was never achieved in previous treatment; MR or above was achieved in previous treatment, but disease progression occurred during subsequent treatment or within 60 days after the last treatment.

Exclusion Criteria

•Any one of the following conditions cannot be selected as a subject：
•Accompanied by other uncontrolled malignancies;
•Subjects with positive Hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb) and peripheral blood Hepatitis B virus(HBV) DNA titer is ≥500IU/mL; hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; human immunodeficiency virus(HIV) antibody positive; syphilis primary screening antibody positive;
•Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure （New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease;
•Patients who are accounted to be not appropriate for this trail by investigator;
•Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;
•Received CAR-T treatment or other gene therapies before enrollment;
•Those who failed to sign informed consent form or comply with the research procedures; Unwilling or unable to comply with research requirements;
•Have had severe immediate hypersensitivity reactions to any drugs used in this research;
•Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment;

Arms & Interventions

Human Derived anti-BCMA CAR-T Injection

Single administration：1.0×10\^6 CAR+T, 3.0×10\^6 CAR+T, 6.0×10\^6 CAR+T

Intervention: Human Derived anti-BCMA CAR-T Injection

Outcomes

Primary Outcomes

Dose limited toxicity(DLT)

Time Frame: 28 days post infusion

Safety Indicator

Secondary Outcomes

Pharmacokinetics parameters -Time to peak CAR level in blood (Tmax)(2 years post infusion)
Pharmacodynamics characteristics -Clonal bone marrow plasma cells level(2 years post infusion)
Number of Subjects with Adverse Events(2 years post infusion)
Change from Baseline in Physical Exam(2 years post infusion)
Pharmacokinetics parameters - Maximum CAR level in blood and CAR level in bone marrow(Cmax)(2 years post infusion)
Pharmacokinetics parameters - 28-day Area under the curve of the CAR level in blood(AUC0-28)(2 years post infusion)
Pharmacodynamics characteristics - Cytokines Concentrations,cytokines level in blood(2 years post infusion)
Percentage of Subjects With Negative Minimal Residual Disease (MRD)(2 years post infusion)
Duration of Subjects With Negative Minimal Residual Disease (MRD)(2 years post infusion)
Change from Baseline in Perform Status as Measured by Eastern Cooperative Oncology Group（ECOG）Score（0-4）(2 years post infusion)
Overall Response Rate (ORR) at 3 month post infusion(3 month post infusion)
Overall Survival (OS)(2 years post infusion)
Change from Baseline in complete blood count with differential and blood biochemical examination(2 years post infusion)
Progression-free Survival (PFS)(2 years post infusion)
Duration of Response (DOR)(2 years post infusion)