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Clinical Study of the Safety and Efficacy of BCMA CAR-NK

Early Phase 1
Recruiting
Conditions
Immunotherapy
Multiple Myeloma
Interventions
Drug: Chimeric Antigen Receptor NK Cell Injection Targeting BCMA (BCMA CAR-NK)
Registration Number
NCT05652530
Lead Sponsor
Shenzhen Pregene Biopharma Co., Ltd.
Brief Summary

The goal of this clinical trial is to study of the Safety and Efficacy of Chimeric Antigen Receptor NK Cell Injection Targeting BCMA (BCMA CAR-NK) in Patients with Relapsed/Refractory Multiple Myeloma

Primary Endpoints:

To evaluate the safety and tolerability of patients with relapsed/refractory multiple myeloma (RR/MM) after BCMA CAR-NK infusion.

To determine the maximum tolerated dose (MTD) and/or subsequent recommended dose (RD) of BCMA CAR-NK in patients with RR/MM.

Secondary Endpoints:

To preliminarily evaluate the effectiveness of BCMA CAR-NK in patients with RR/MM.

To preliminarily evaluate the pharmacokinetic parameters of BCMA CAR-NK cells in patients with RR/MM.

To preliminarily evaluate BCMA CAR-NK cell survival in subjects blood in relation to efficacy, adverse events and relevant biomarker levels.

To preliminarily evaluate the relationship between donors and subjects KIR-Ligand mismatch and safety \& efficacy.

To preliminarily evaluate the impact of the degree of HLA genotype matching between donors and subjects on the survival of BCMA CAR-NK cells in the subjects blood.

Subjects are enrolled and treated with lymphocyte clearance chemotherapy (including pre-clearance evaluation), pre-infusion evaluation and BCMA CAR-NK cells infusion and enter the follow-up period after the end of the DLT observation period.

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
19
Inclusion Criteria
  • Age 18 years or above, no gender preference.
  • Patients who have received at least 3 prior lines of treatment for multiple myeloma and have failed at least proteasome inhibitor and immunomodulator therapy; Each line has at least 1 complete treatment cycle unless the best remission status for that treatment is documented as progressive disease (PD) (as per the IMWG efficacy evaluation criteria published in 2016, Appendix 4); PD must be documented during or within 12 months after receiving the last treatment.
  • Presence of measurable lesions at screening, which are defined as any of the following situations:

Serum M protein≥1 g/dL (≥10 g/L) Urinary M protein≥200 mg/24 hours Serum free light chain (FLC): abnormal serum FLC ratio (<0.26 or >1.65) and involved FLC≥10 mg/dL (100 mg/L)

  • ECOG score (Appendix 1): 0~1.
  • Expected survival≥3 months.
  • The following test values within 7 days prior to lymphocyte clearance meet the following criteria:

Hematology Absolute lymphocyte count:≥0.5×109/L[Granulocyte colony-stimulating factor (G-CSF) is allowed, but subjects should not have received this supportive therapy within 7 days prior to laboratory test during the screening period] Absolute neutrophil count:≥1.0×10^9 /L[Granulocyte colony-stimulating factor (G-CSF) is allowed, but subjects should not have received this supportive therapy within 7 days prior to laboratory test during the screening period].

Platelets:Subjects platelet count ≥50 x 10^9/L (subjects must not receive transfusion support within 7 days prior to laboratory test during the screening period) Hemoglobin:≥8.0 g/dL (recombinant human erythropoietin is allowed) [subjects have not received a red blood cell (RBC) transfusion within 7 days prior to laboratory test during the screening period].

Liver Total bilirubin (serum) :Total bilirubin (serum) ≤1.5 × ULN AST and ALT:≤3× ULN

  • Peripheral venous pathway meets the requirements of intravenous drip.
  • Subjects agree to use reliable methods for contraception from the time of signing the informed consent till 1 year after the transfusion.
  • Voluntary participation in the clinical trial and signing of the informed consent form.
Exclusion Criteria
  • Subjects who have had a severe anaphylactic reaction.
  • Subjects who received the following anti-MM therapy within a specific time prior to lymphocyte clearance.

Small molecule targeted therapy within 2 weeks or 5 half-lives (whichever is longer).

Large-molecule drug within 4 weeks or 2 half-lives (whichever is longer). Cytotoxic drugs, modern Chinese medicine preparations with antitumor effects within 2 weeks.

Immunomodulators therapy within 1 week.

  • Subjects who have received a live or attenuated vaccine within 4 weeks prior to lymphocyte clearance.
  • Subjects who have received the following therapy within 7 days prior to lymphocyte clearance, or that requires long-term treatment during the study period according to the investigators:

Systemic steroid therapy (except for inhaled one or topical use). Immunosuppressive therapy. Treatment of graft-versus-host response.

  • Subjects presenting with incomplete recovery or stabilization to grade 1 (NCI-CTCAE v5.0) of toxicity (including peripheral neuropathy) caused by prior treatments.
  • Cardiac disease: episode of myocardial infarction≤6 months prior to lymphocyte clearance; episode of unstable angina, severe arrhythmia as judged by the investigators, or coronary artery bypass graft≤3 months prior to lymphocyte clearance.
  • Women who are pregnant or breastfeeding.
  • Subjects who, in the opinion of the investigators, have any clinical or laboratory test abnormalities or other reasons that make them ineligible to participate in this clinical study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
BCMA CAR-NKChimeric Antigen Receptor NK Cell Injection Targeting BCMA (BCMA CAR-NK)-
Primary Outcome Measures
NameTimeMethod
Safety and Toxicity Assessment per Adverse Event reporting classified according to CTCAE V5.0Day 28

per Adverse Event reporting classified according to CTCAE V5.0

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Henan Cancer Hospital

🇨🇳

Zhengzhou, Henan, China

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