Clinical trial NCT05302648: To Evaluate the Safety and Efficacy of Human Derived Anti-BCMA CAR-T Injection for Subjects with R/R MM
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Multiple Myeloma
Keywords: BCMA
CAR-T
multiple myeloma
Relapsed /Refractory
Lead sponsor: Hrain Biotechnology Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Shanghai Changzheng Hospital
First posted: 2022-03-31
Enrollment: 18
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: 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.

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:

  1. 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.
  2. Urine M protein ≥ 200 mg/24h;
  3. 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.
* ECOG score 0-2;
* Liver, kidney and cardiopulmonary functions meet the following requirements:

  1. Creatinine clearance (estimated by Cockcroft Gault formula) ≥ 40 mL/min;
  2. Left ventricular ejection fraction \>50%;
  3. Baseline peripheral oxygen saturation \>95%;
  4. Total bilirubin ≤ 2×ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × ULN;
* The venous access required for collection can be established and leukepheresis can be carriedaccording 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 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;
* 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.

Primary outcomes:
measure: Dose limited toxicity(DLT)
timeFrame: 28 days post infusion
Secondary outcomes:
measure: Pharmacokinetics parameters - Maximum CAR level in blood and CAR level in bone marrow(Cmax)
timeFrame: 2 years post infusion
measure: Pharmacokinetics parameters -Time to peak CAR level in blood (Tmax)
timeFrame: 2 years post infusion
measure: Pharmacokinetics parameters - 28-day Area under the curve of the CAR level in blood(AUC0-28)
timeFrame: 2 years post infusion
measure: Pharmacodynamics characteristics - Cytokines Concentrations,cytokines level in blood
timeFrame: 2 years post infusion
measure: Pharmacodynamics characteristics -Clonal bone marrow plasma cells level
timeFrame: 2 years post infusion
measure: Overall Response Rate (ORR) at 3 month post infusion
timeFrame: 3 month post infusion
measure: Percentage of Subjects With Negative Minimal Residual Disease (MRD)
timeFrame: 2 years post infusion
measure: Duration of Subjects With Negative Minimal Residual Disease (MRD)
timeFrame: 2 years post infusion
measure: Number of Subjects with Adverse Events
timeFrame: 2 years post infusion
measure: Change from Baseline in Perform Status as Measured by Eastern Cooperative Oncology Group（ECOG）Score（0-4）
timeFrame: 2 years post infusion
measure: Change from Baseline in complete blood count with differential and blood biochemical examination
timeFrame: 2 years post infusion
measure: Change from Baseline in Physical Exam
timeFrame: 2 years post infusion
measure: Progression-free Survival (PFS)
timeFrame: 2 years post infusion
measure: Overall Survival (OS)
timeFrame: 2 years post infusion
measure: Duration of Response (DOR)
timeFrame: 2 years post infusion
Other outcomes:
measure: Distribution of CAR-T
timeFrame: 2 years post infusion
measure: Cytokines Concentrations
timeFrame: 2 years post infusion
measure: Different Expression Genes (DEGs) in Plasma Cells for Relapse Subjects as Measured by Single-cell Ribonucleic Acid (RNA) Sequencing.
timeFrame: 2 years post infusion
Locations:
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
Study officials:
affiliation: Shanghai Changzheng Hospital
name: Juan Du, Doctor
role: PRINCIPAL_INVESTIGATOR
References: