An Clinical Study of NKG2D-CAR-NK Cells for the Treatment of Refractory Recurrent Multiple Myeloma

NCT06379451 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: [2023]YLJSA088
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Multiple myeloma (MM) is a malignant disease characterized by the abnormal proliferation of clonal plasma cells. However, multiple myeloma remains an incurable disease and requires the exploration of more effective treatment methods to improve the efficacy of relapsed refractory multiple myeloma and prolong survival time.Currently, clinical application of CAR-T is mostly based on autologous T cell preparation, while relapsed/refractory AML patients have undergone multiple chemotherapy treatments, resulting in impaired self-T cell function, which affects the efficacy and prognosis of CAR-T therapy. Therefore, it is necessary to find new alternative treatments. NK cells are important immune cells in the body and are an important component of innate immunity. Compared with CAR-T cell therapy, CAR-NK cells have unique advantages in adoptive cell therapy. NKG2D receptor is an activating receptor expressed on NK cells, which can recognize NKG2D ligands (NKG2DL) expressed on tumor cells, activating NK cell killing activity through NKG2D-NKG2DL interaction. Therefore, the investigators plan to treat relapsed multiple myeloma by infusing NKG2D-CAR-NK cells to evaluate its efficacy and safety.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose Limiting Toxicity (DLTs)

  To characterize the Dose Limiting Toxicities (DLTs) of NKG2D-CAR-NK Cells for refractory recurrent multiple myeloma

  within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion

• Treatment Emergent Adverse Events (TEAEs)

  To characterize the Treatment Emergent Adverse Events (TEAEs) of NKG2D-CAR-NK Cells for refractory recurrent multiple myeloma

  within 4 weeks after infusion; 12, 24, 36 and 52 weeks after infusion

Secondary Outcomes (1)

• Objective Response Rate of subjects

  Time Frame: 2, 4, 8, 12, 16, 24, 28, 40 and 52 weeks after first infusion

Study Arms (3)

Low dose group

EXPERIMENTAL

CAR-NK cell count 6x10\^8

Drug: NKG2D Chimeric Antigen Receptor NK Cell Injection

Medium dose group

EXPERIMENTAL

CAR-NK cell count 1x10\^9

Drug: NKG2D Chimeric Antigen Receptor NK Cell Injection

High dose group

EXPERIMENTAL

CAR-NK cell count 1.5x10\^9

Drug: NKG2D Chimeric Antigen Receptor NK Cell Injection

Interventions

NKG2D Chimeric Antigen Receptor NK Cell Injection DRUG

Administer KN1102 cell injection three times on day 0, day 7, and day 14, respectively.

Also known as: KN1102 cell injection

High dose group; Low dose group; Medium dose group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age range from 18 to 70 years old;
• Expected survival time\>12 weeks;
• Diagnosed as multiple myeloma through physical examination, pathological examination, laboratory examination, and imaging;
• Difficult to treat multiple myeloma patients;
• Patients with recurrent multiple myeloma;
• ALT, AST\<3 times normal; Bilirubin\<2.0mg/dl;
• Quality of Life Score (KPS)\>50%;
• The patient has no serious diseases such as heart, liver, or kidney;
• Recurrence or no remission of the disease after hematopoietic stem cell transplantation or cellular immunotherapy;
• Inappropriate conditions for stem cell transplantation or abandonment of transplantation due to limitations in conditions;
• Blood can be taken intravenously without any other contraindications for leukocyte removal surgery;
• Can understand and voluntarily sign a written informed consent form.

You may not qualify if:

• Pregnant or lactating women, or women with pregnancy plans within six months;
• Infectious diseases (such as HIV, active tuberculosis, etc.);
• Active hepatitis B or hepatitis C infection;
• Feasibility assessment screening proves that the transfection of targeted lymphocytes is less than 10% or the amplification is insufficient (\<5-fold) under the co stimulation of CD3/CD28;
• Abnormal vital signs and inability to cooperate with the examination;
• Individuals with mental or psychological disorders who cannot cooperate with treatment and efficacy evaluation;
• Highly allergic constitution or a history of severe allergies, especially those who are allergic to IL-2;
• Subjects with systemic or severe local infections requiring anti infection treatment;
• Subjects with severe autoimmune diseases;
• The doctor believes that there are other reasons why patients cannot be included in treatment.

Sponsors & Collaborators

• Changzhou No.2 People's Hospital: lead

Study Sites (1)

Changzhou Second People's Hospital

Changzhou, Jiangsu, 213000, China

Location

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Xuzhang Lu, doctor

  The Second People's Hospital of Changzhou

  STUDY DIRECTOR

• Liming Tang, doctor

  The Second People's Hospital of Changzhou

  STUDY CHAIR

Central Study Contacts

Wei Qin, doctor

CONTACT

+8618796912763; qinwei19840601@163.com

Xuzhang Lu, doctor

CONTACT

+8615295189493; luxuzhang2022@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Hematology Department

Study Record Dates

• First Submitted: April 17, 2024
• First Posted: April 23, 2024
• Study Start: April 18, 2024
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: April 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)