A Early Phase 1 Clinical Trial to Evaluate the Safety and Efficacy of Human BCMA Targeted CAR-NK Cells Injection for Subjects With Relapsed/Refractory Multiple Myeloma or Plasma Cell Leukemia

Hrain Biotechnology Co., Ltd.1 site in 1 country18 target enrollmentJuly 4, 2023

ConditionsMultiple Myeloma Plasma Cell Leukemia

InterventionsHuman BCMA targeted CAR-NK cells injection

DrugsHuman BCMA targeted CAR-NK cells injection

Overview

Phase: Early Phase 1
Intervention: Human BCMA targeted CAR-NK cells injection
Conditions: Multiple Myeloma
Sponsor: Hrain Biotechnology Co., Ltd.
Enrollment: 18
Locations: 1
Primary Endpoint: Dose limited toxicity (DLT)
Status: Recruiting
Last Updated: 2 years ago

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 BCMA targeted CAR-NK Cells injection, and to preliminarily observe the efficacy of the trial drug in patients with relapsed/refractory multiple myeloma or plasma cell leukemia.

Detailed Description

Subjects with relapsed/refractory multiple myeloma or plasma cell leukemia 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 preconditioning chemotherapy prior to the first infusion of human BCMA targeted CAR-NK Cells injection. After the infusion, subjects will be followed for adverse events, pharmacokinetic/pharmacodynamics characteristics, efficacy of human BCMA targeted CAR-NK cells. Study procedures may be performed while hospitalized.

Registry

clinicaltrials.gov

Start Date

July 4, 2023

End Date

September 30, 2027

Last Updated

2 years ago

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 trials, understand and sign the informed consent document, be willing to complete all the trial procedures;
•18 years and older, Male and female;
•Expected survival \> 12 weeks;
•Documented evidence of multiple myeloma at diagnosis as defined by IMWG updated criteria (2014), or plasma cell leukemia at diagnosis as defined by Diagnosis and therapeutic criteria of hematologic disease (4th edition);
•One of the following indicators is satisfied:
•Serum M protein: IgG M protein ≥5 g/L; or IgA M protein ≥5 g/L; or IgD M protein and IgD \>ULN;
•Urine M protein ≥200 mg/24h;
•Affected serum free light chain ≥100 mg/L and Serum free light chain ratio is abnormal;
•Clonal bone marrow plasma cells ≥10 % for non-secretory myeloma;

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 hepatitis B virus (HBV) DNA titers higher than the lower limit of the normal range of the investigative site; Hepatitis C virus (HCV) antibody positive and peripheral blood HCV RNA positive; Human Immunodeficiency Viral (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;
•Subjects who are considered unsuitable to participate in this trial by the 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-NK treatment or other gene therapies before enrollment;
•Subjects who have a disease that affects the signing of written informed consent or who are unable to comply with research procedures; or who are unwilling or unable to comply with research requirements;
•Subjects who 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 BCMA Targeted CAR-NK Cells Injection

Two doses on Day 0 and Day 7. 1.5×10\^8 CAR+NK cells/dose, 3.0×10\^8 CAR+NK cells/dose or 6.0×10\^8 CAR+NK cells/dose

Intervention: Human BCMA targeted CAR-NK cells injection

Outcomes

Primary Outcomes

Dose limited toxicity (DLT)

Time Frame: 28 days post infusion

Safety Indicators

Secondary Outcomes

Pharmacokinetics parameters - the highest concentration of human BCMA targeted CAR-NK cells amplified in peripheral blood and bone marrow after infusion(2 years post infusion)
Pharmacokinetics parameters - the time to reach the highest concentration of human BCMA targeted CAR-NK cells amplified in peripheral blood and bone marrow after infusion(2 years post infusion)
Pharmacokinetics parameters - the 28-day area under the curve of human BCMA targeted CAR-NK cells amplified in peripheral blood and bone marrow after infusion(2 years post infusion)
Change in body weight over time after infusion(2 years post infusion)
Pharmacodynamics characteristics - the detection values of monoclonal plasma cell in bone marrow(2 years post infusion)
Pharmacodynamics characteristics - the detection values of CRP, IL-6, IL-15, Granzyme B cytokines in peripheral blood(2 years post infusion)
Percentage of subjects with negative minimal residual disease (MRD)(2 years post infusion)
Number of subjects with adverse events(2 years post infusion)
Overall Survival (OS) after administration(2 years post infusion)
Overall response rate (ORR, include PR, VGPR, CR and sCR) after administration(3 months post infusion)
Duration of subjects with negative minimal residual disease (MRD)(2 years post infusion)
Change from baseline in perform status as measured by Easten Cooperative Oncology Group (ECOG) score(Safety Metrics)
The occurrence rate of adverse events grade≥3 assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.(2 years post infusion)
Duration of remission (DOR) after administration(2 years post infusion)