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

Clinical 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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma; Immunotherapy
• Intervention / Treatment: Drug: Chimeric Antigen Receptor NK Cell Injection Targeting BCMA (BCMA CAR-NK)

• Study Type: Interventional
• Enrollment (Anticipated): 19
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• China
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Recruiting
      • Henan Cancer Hospital
      • Contact: Baijun Fan; Phone Number: 13526607830; Email: fdation@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 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: BCMA CAR-NK

Drug: Chimeric Antigen Receptor NK Cell Injection Targeting BCMA (BCMA CAR-NK); This product is allogeneic NK cells which are cryopreserved after in vitro CAR genetic modification and scale-up manufacturing. Subjects are enrolled and treated with lymphocyte clearance chemotherapy (including pre-clearance evaluation), pre-infusion evaluation and BCMA CAR-NK cells infusion.; Other Names: Lymphocyte clearance

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Toxicity Assessment per Adverse Event reporting classified according to CTCAE V5.0	per Adverse Event reporting classified according to CTCAE V5.0	Day 28

Collaborators and Investigators

• Sponsor: Shenzhen Pregene Biopharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2022
• Primary Completion (Anticipated): September 30, 2023
• Study Completion (Anticipated): November 30, 2023

Study Registration Dates

• First Submitted: November 28, 2022
• First Submitted That Met QC Criteria: December 14, 2022
• First Posted (Estimate): December 15, 2022

Study Record Updates

• Last Update Posted (Estimate): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 14, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• 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: PRG2101

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