Human BCMA Targeted T Cells Injection（BCMA CAR-T）for Subjects With R/R MM

A Phase Ⅱ Clinical Study Evaluating the Efficacy and Safety of Human BCMA Targeted T Cells Injection Therapy for Relapsed/Refractory Multiple Myeloma

A Phase Ⅱ Clinical Study Evaluating the Efficacy and Safety of Human BCMA Targeted T Cells Injection（BCMA CAR-T） Therapy for R/R MM.

Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of BCMA CAR+ T cells.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Human BCMA Targeted T Cells Injection

Detailed Description

Participants with relapsed/refractory multiple myeloma can participate if all eligibility criteria are met. Tests required to determine eligibility include disease assessments, a physical exam, Electrocardiograph, Computedtomography （CT）/Magnetic Resonance Imaging(MRI)/Positron Emission Tomography（PET）, and blood draws. Participants receive chemotherapy prior to the infusion of BCMA CAR+ T cells. After the infusion, participants will be followed for side effects and effect of BCMA CAR+ T cells. Study procedures may be performed while hospitalized.

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xuedong Sun, M.D.; Phone Number: +8615811287219; Email: sunxuedong@dashengbio.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200003
      • Recruiting
      • Shanghai Changzheng Hospital
      • Contact: Juan Du, Ph.D.; Phone Number: 021-81885423; Email: juan_du@live.com
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • Recruiting
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Songfu Jiang, Professor; Phone Number: +8615305770033; Email: Jiangsongfu@189.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)，gender is not limited;
• Expected survival > 12 weeks;
• Previously diagnosed as multiple myeloma by the International Myeloma Working Group（IMWG） updated criteria;

• One of the following indicators is satisfied:

  1. Serum M protein ≥ 5 g/L;
  2. Urine M protein ≥ 200 mg/24h;
  3. Affected serum free light chain ≥ 100 mg/L and Serum free light chain ratio is abnormal ;

• Patients with relapsed/refractory multiple myeloma, satisfying:

  1. Patients have received at least 3 prior MM treatment regimens containing at least one proteasome inhibitor and one immunomodulator;
  2. Progress is documented within 12 months of the most recent antimyeloma treatment, or efficacy assessment does not reach minimal response(MR) or above or progression within 60 days of the most recent antimyeloma treatment;
• ECOG score 0-2;
• Autologous hematopoietic stem cell transplantation is not possible or relapses after autologous hematopoietic stem cell transplantation, but requires further treatment at the investigator's discretion；

• Liver, kidney and cardiopulmonary functions meet the following requirements:

  1. Creatinine clearance rate (estimated by CockcroftGault formula)≥40mL/min;
  2. Total bilirubin≤2×ULN; Alanine aminotransferase (ALT) ≤2.5×ULN and aspartate aminotransferase (AST)≤2.5×ULN;
  3. Left ventricular ejection fraction >50%;
  4. Baseline peripheral oxygen saturation>95%;
• The venous access required for collection can be established, no contraindications to leukocyte collection, and leukepheresis can be carried according to the judgement of investigators, satisfying hemoglobin≥70g/L,platelets ≥50×10^9 / L, neutrophils ≥1.0×10^9/L.

Exclusion Criteria:Any one of the following conditions cannot be selected as a subject：

• Subjects have a history of central nervous system (CNS) diseases such as seizures, paralysis, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, psychosis; known or history of active central nervous system (CNS) involvement or presentation of multiple myeloma meninge/meningeal involvement;
• Subjects with plasma cell leukemia, Waldenstrom's macroglobulinemia, POEMS syndrome, or primary light chain amyloidosis;
• Accompanied by other uncontrolled malignancies, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, ductal carcinoma in situ after radical resection and thyroid cancer after radical resection ;
• Any uncontrollable active infection, including but not limited to active tuberculosis; fungal, bacterial, viral, or other infections that are uncontrollable or require systemic intravenous therapy are present or suspected within 14 days prior to enrollment;
• 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 positive;
• Any uncontrolled systemic diseases, including but not limited to unstable angina pectoris, 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), uncontrolled diabetes mellitus (glycosylated hemoglobin HbAlc >8% at screening)，severe arrhythmia, liver, kidney, or metabolic diseases that are poorly controlled by medications;
• Subjects who have a history of pacemaker and brain pacemaker implantation;
• Subjects who have received CAR-T treatment or other genetically modified cell therapies, as well as other BCMA-targeting drugs;
• Subjects with any hematopoietic stem cell transplant performed within the first two months of screening, or any immunosuppressive therapy due to graft-versus-host disease performed during the screening period;
• Subjects who were receiving systemic steroid treatment within 14 days before the screening period and who were judged by the investigator to require long-term use of systemic steroid therapy during treatment (except inhalation or topical use); or subjects who received any systemic anti-tumor therapy ( except for local anti-tumor therapy) ;
• Subjects who have received live attenuated vaccine within 4 weeks prior to apheresis;
• 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;
• Pregnant or lactating woman, or planned pregnancy during treatment or within 1 year after treatment, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion; except participants of childbearing age are willing to use a very effective and reliable method of contraception for 1 year after study treatment;
• 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;
• Subjects who are considered unsuitable to participate in this trial by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Human BCMA Targeted T Cells Injection; Single administration：6.0×10^6 CAR+T/kg	Drug: Human BCMA Targeted T Cells Injection; A single dose of predetermined level CAR-positive T cells will be infused.; Other Names: BCMA CAR-T

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) at 3 months post infusion as evaluated by the Independent Review Committee	ORR at 3 months post infusion as evaluated by the Independent Review Committee (IRC) includes stringent complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR).	3 months post infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of remission (DOR) after administration	DOR refers to the time from the first assessment of the tumor for complete response and above efficacy to the first assessment of disease progression or death of any cause;	2~3 years post infusion
Progression-free Survival (PFS) after administration	PFS refers to the time from the start of cell infusion to the first assessment of tumor progression or death from any cause;	2~3 years post infusion
Overall Survival (OS) after administration	OS refers to the time from cell infusion to death due to any cause;	2~3 years post infusion
Objective Response Rate (ORR) at 3 months post infusion as evaluated by the Investigator	ORR at 3 months post infusion as evaluated by the Investigator;	3 months post infusion
Objective Response Rate (ORR) at 6 months post infusion as evaluated by the Independent Review Committee	ORR at 6 months post infusion as evaluated by the Independent Review Committee (IRC)；	6 months post infusion
Percentage of Subjects With Negative Minimal Residual Disease (MRD)	MRD negative rate is defined as the proportion of subjects who achieve MRD negative status;	2~3 years post infusion
Duration of Subjects With Negative Minimal Residual Disease (MRD)	MRD duration will calculated among MRD negative responders fom the date of initial MRD negative to the date of first documented evidence of MRD positive, as defined in the International Myeloma Working Group（IMWG） criteria (2016);	2~3 years post infusion
Number of Subjects with Adverse Events	Adverse event is any untoward medical event that occurs in a subject administered an investigational drug.	2~3 years post infusion
Change from Baseline in Perform Status as Measured by Eastern Cooperative Oncology Group（ECOG）Score（0-2）	Eastern Cooperative Oncology Group（ECOG） Performance Status Score（0-2） will be assessed by the inverstigator at baseline and the respective time point, higher scores mean a worse performance status.	2~3 years post infusion
The occurrence rate of adverse events grade ≥ 3 assessed by Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.	Safety Indicators	2~3 years post infusion
Change in body weight over time after reinfusion	Safety Indicators	2~3 years post infusion
Pharmacokinetic indicators:Maximum CAR level inperipheral blood or bone marrow (Cmax)	The highest concentration of Human BCMA Targeted T Cells Injection amplified in peripheral blood or bone marrow after infusion (Cmax) ；	2~3 years post infusion
Pharmacokinetic indicators: Time to peak CAR level in blood or bone marrow (Tmax)	The time to reach the highest concentration of Human BCMA Targeted T Cells Injection in peripheral blood or bone marrow after infusion (Tmax) ；	2~3 years post infusion
Pharmacokinetic indicators: 28-day Area under the curve of the CAR level in blood or bone marrow (AUC0-28d)	The 28-day area under the curve of Human BCMA Targeted T Cells Injection in peripheral blood or bone marrow after infusion（AUC0-28d）；	2~3 years post infusion
Pharmacodynamic indicators: the concentration level of soluble BCMA (sBCMA) in peripheral blood	The concentration level of soluble BCMA (sBCMA) in peripheral blood at various time points after infusion of Human BCMA Targeted T Cells Injection；	2~3 years post infusion
Pharmacodynamic indicators: the concentration level of CAR-T cell-related serum cytokines such as C-Reactive Protein（CRP） in peripheral blood；	Effectiveness Metrics	2~3 years post infusion
Pharmacodynamic indicators: the concentration level of CAR-T cell-related serum cytokines such as Interleukin-6（IL-6）, IL-2, IL-10, Tumor Necrosis Factor （TNF-α），Interferon-γ（IFN-γ）in peripheral blood；	Effectiveness Metrics	2~3 years post infusion
Immunogenicity: Anti-drug antibody(ADA) positive ratio	Immunogenicity study evaluated the immune responses to anti-BCMA scFV including the detection of anti-scFV antibodies；	2~3 years post infusion
Immunogenicity: Neutralizing Antibody(Nab) positive ratio	Immunogenicity study evaluated the immune responses to anti-BCMA scFV including the detection of neutralizing antibodies (NAbs) against scFV.	2~3 years post infusion

Collaborators and Investigators

• Sponsor: Hrain Biotechnology Co., Ltd.
• Collaborators: First Affiliated Hospital of Wenzhou Medical University; Shanghai Changzheng Hospital
• Investigators: Principal Investigator: Juan Du, Ph.D., Shanghai Changzheng Hospital; Principal Investigator: Songfu Jiang, Professor, First affiliated hospital of Wenzhou medical university

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2022
• Primary Completion (Anticipated): July 31, 2025
• Study Completion (Anticipated): July 31, 2027

Study Registration Dates

• First Submitted: October 18, 2022
• First Submitted That Met QC Criteria: October 21, 2022
• First Posted (Actual): October 26, 2022

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: Multiple Myeloma; CAR-T; Relapsed/Refractory; BCMA
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: HRAIN01-MM01-Ⅱ

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No