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To Evaluate the Safety and Efficacy of Human BCMA Targeted CAR-NK Cells Injection for Subjects With R/R MM or PCL

Primary Purpose

Multiple Myeloma, Plasma Cell Leukemia

Status
Recruiting
Phase
Early Phase 1
Locations
China
Study Type
Interventional
Intervention
Human BCMA targeted CAR-NK cells injection
Sponsored by
Hrain Biotechnology Co., Ltd.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma focused on measuring BCMA, CAR-NK, Multiple Myeloma, Plasma Cell Leukemia, Relapsed /Refractory

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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; Patients with relapsed/refractory multiple myeloma or plasma cell leukemia, satisfying: Patients have received at least 3 prior MM or PCL treatment regimens containing at least one proteasome inhibitor and one immunomodulatory; Progress is documented within 60 days of the most recent anti-tumor treatment, or efficacy assessment does not reach minimal response(MR) or above; Liver, kidney and cardiopulmonary functions meet the following requirements: Creatinine clearance rate (estimated by CockcroftGault formula) ≥30mL/min; Left ventricular ejection fraction > 50%; Baseline peripheral oxygen saturation > 95%; Total bilirubin≤ 2×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; Blood routine examination satisfying hemoglobin≥60 g/L, neutrophils≥ 1.0×10^9/L, and platelets≥30×10^9/L, can complete this trial according to the judgement of investigators. 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; In the past two years, the terminal organ was damaged due to autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required; Patients with symptoms of central nervous system.

Sites / Locations

  • Shanghai Changzheng HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Human BCMA Targeted CAR-NK Cells Injection

Arm Description

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

Outcomes

Primary Outcome Measures

Dose limited toxicity (DLT)
Safety Indicators

Secondary Outcome Measures

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

Full Information

First Posted
September 13, 2023
Last Updated
September 13, 2023
Sponsor
Hrain Biotechnology Co., Ltd.
Collaborators
Shanghai Changzheng Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT06045091
Brief Title
To Evaluate the Safety and Efficacy of Human BCMA Targeted CAR-NK Cells Injection for Subjects With R/R MM or PCL
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 4, 2023 (Actual)
Primary Completion Date
September 30, 2025 (Anticipated)
Study Completion Date
September 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hrain Biotechnology Co., Ltd.
Collaborators
Shanghai Changzheng Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Plasma Cell Leukemia
Keywords
BCMA, CAR-NK, Multiple Myeloma, Plasma Cell Leukemia, Relapsed /Refractory

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Human BCMA Targeted CAR-NK Cells Injection
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
Human BCMA targeted CAR-NK cells injection
Other Intervention Name(s)
BCMA CAR-NK
Intervention Description
Allogenic genetically modified anti-BCMA CAR transduced NK cells
Primary Outcome Measure Information:
Title
Dose limited toxicity (DLT)
Description
Safety Indicators
Time Frame
28 days post infusion
Secondary Outcome Measure Information:
Title
Pharmacokinetics parameters - the highest concentration of human BCMA targeted CAR-NK cells amplified in peripheral blood and bone marrow after infusion
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
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
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
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
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Pharmacodynamics characteristics - the detection values of CRP, IL-6, IL-15, Granzyme B cytokines in peripheral blood
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Pharmacodynamics characteristics - the detection values of monoclonal plasma cell in bone marrow
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Overall response rate (ORR, include PR, VGPR, CR and sCR) after administration
Description
Effectiveness Metrics
Time Frame
3 months post infusion
Title
Percentage of subjects with negative minimal residual disease (MRD)
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Duration of subjects with negative minimal residual disease (MRD)
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Number of subjects with adverse events
Description
Safety Metrics
Time Frame
2 years post infusion
Title
Change from baseline in perform status as measured by Easten Cooperative Oncology Group (ECOG) score
Description
2 years post infusion
Time Frame
Safety Metrics
Title
The occurrence rate of adverse events grade≥3 assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.
Description
Safety Metrics
Time Frame
2 years post infusion
Title
Change in body weight over time after infusion
Description
Safety Metrics
Time Frame
2 years post infusion
Title
Duration of remission (DOR) after administration
Description
Effectiveness Metrics
Time Frame
2 years post infusion
Title
Overall Survival (OS) after administration
Description
Effectiveness Metrics
Time Frame
2 years post infusion

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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; Patients with relapsed/refractory multiple myeloma or plasma cell leukemia, satisfying: Patients have received at least 3 prior MM or PCL treatment regimens containing at least one proteasome inhibitor and one immunomodulatory; Progress is documented within 60 days of the most recent anti-tumor treatment, or efficacy assessment does not reach minimal response(MR) or above; Liver, kidney and cardiopulmonary functions meet the following requirements: Creatinine clearance rate (estimated by CockcroftGault formula) ≥30mL/min; Left ventricular ejection fraction > 50%; Baseline peripheral oxygen saturation > 95%; Total bilirubin≤ 2×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5×ULN; Blood routine examination satisfying hemoglobin≥60 g/L, neutrophils≥ 1.0×10^9/L, and platelets≥30×10^9/L, can complete this trial according to the judgement of investigators. 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; In the past two years, the terminal organ was damaged due to autoimmune diseases (such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus), or the systemic use of immunosuppressive or other systemic disease control drugs was required; Patients with symptoms of central nervous system.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Xuedong Sun, Doctor
Phone
+8615811287219
Email
sunxuedong@dashengbio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Juan Du, Doctor
Organizational Affiliation
Shanghai Changzheng Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shanghai Changzheng Hospital
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200003
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Juan Du, Doctor
Phone
0086-021-81885423
Email
juan_du@live.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

To Evaluate the Safety and Efficacy of Human BCMA Targeted CAR-NK Cells Injection for Subjects With R/R MM or PCL

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