Safety and Efficacy of Anti-FcRL5 CAR-T Cell Therapy in Treating Relapsed and Refractory Multiple Myeloma (R/R MM)

Efficacy and Safety Study of Anti-FcRL5 CAR-T Cells in Subjects With Relapsed and Refractory Multiple Myeloma

This is an open label, single-arm, Phase 2 study to evaluate the efficacy and safety of Anti-FcRL5 CAR-T in subjects with relapsed and refractory multiple myeloma. A leukapheresis procedure will be performed to manufacture. Anti-FcRL5 chimeric antigen receptor (CAR) modified T cells. Prior to Anti-FcRL5 infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: anti-FcRL5 CAR-T

Detailed Description

This open label, single-arm, Phase 2 study aims to evaluate the efficacy and safety of Anti-FcRL5 CAR-T in subjects with relapsed and refractory multiple myeloma. A leukapheresis procedure will be performed to manufacture. Anti-FcRL5 chimeric antigen receptor (CAR) modified T cells. Prior to Anti-FcRL5 infusion subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide. After infusion, the investigators will observe the characteristics of dose limited toxicity (DLT), and determine the maximum tolerable agent MTD and rp2d were confirmed. To provide basis for the dosage and treatment plan of cell products in follow-up clinical trials.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Kailin Xu, MD.,PD.; Phone Number: PD 15162166166; Email: lihmd@163.com

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221006
      • Recruiting
      • The Affiliated Hospital of Xuzhou Medical University
      • Contact: Kailin Xu, MD; Phone Number: 15162166166; Email: lihmd@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

The set subject inclusion criteria include multiple documents of multiple myeloma, no effective treatment options (e. g. autologous or allogeneic stem cell transplantation) and limited outcome (<2 years) with existing therapies, as follows:

1. Age is 18~70 years old;
2. Expected survival period of>12 weeks;
3. Multiple myeloma was diagnosed by physical examination, pathological examination, laboratory examination and imaging;
4. Patients with refractory multiple myeloma;
5. Patients with multiple myeloma recurrence;
6. ALT and AST <3 times normal; bilirubin <2.0mg / dl;
7. Quality of survival score (KPS)> 50%;
8. The patient has no serious heart, liver, kidney and other diseases;
9. Recurrence or no disease remission after hematopoietic stem cell transplantation or cellular immunotherapy;
10. Is not suitable for stem cell transplantation conditions or to abandon transplantation due to conditional restrictions;
11. Blood can be obtained intravenously, without other contraindications to leukapheresis;
12. Understand and voluntarily sign a written informed consent form.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding, or who have a pregnancy plan within six months;
2. Infectious diseases (such as HIV, active tuberculosis, etc.);
3. Active hepatitis B or hepatitis C infection;
4. Feasibility assessment screening demonstrated <10% transfection of targeted lymphocytes or underamplification under CD3 / CD28 costimulation (<5-fold);
5. Abnormal vital signs, and unable to cooperate with the examination;
6. Have mental or mental illness who cannot cooperate with the treatment and efficacy evaluation;
7. Highly allergic constitution or have a history of severe allergies, especially allergic to IL-2;
8. Subjects with a systemic infection or a severe local infection requiring anti-infective treatment;
9. Subjects with severe autoimmune disease;
10. The doctor believes there were other reasons for inclusion

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: anti FcRL5 CAR-T; anti-FcRL5 autologous CAR T cells will be infused at a dose ranging from 1 - 2 x 10^6/kg CAR+ T cells after receiving lymphodepleting chemotherapy.	Drug: anti-FcRL5 CAR-T; anti-FcRL5 autologous CAR T cells will be infused at a dose ranging from 1 - 2 x 10^6/kg CAR+ T cells after receiving lymphodepleting chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events	Adverse events assessed according to NCI-CTCAE v5.0	Baseline up to 28 days after CAR-T cells infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event-free survival (EFS)	Assessment of EFS at Month 6, 12, 18 and 24	Month 6, 12, 18 and 24
Overall survival (OS)	Assessment of OS at Month 6, 12, 18 and 24	Month 6, 12, 18 and 24
overall response rate (ORR)	Assessment of ORR at Month 6, 12, 18 and 24	Month 6, 12, 18 and 24
complete response (CR)	Assessment of CR at Month 6, 12, 18 and 24	Month 6, 12, 18 and 24

Collaborators and Investigators

• Sponsor: Xuzhou Medical University
• Investigators: Study Chair: Kailin Xu, MD.,PD., The Affiliated Hospital oh Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): December 25, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2028

Study Registration Dates

• First Submitted: December 25, 2023
• First Submitted That Met QC Criteria: December 25, 2023
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: December 25, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Myeloma; FcRL5
• 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: XYFY2023-KL216-01

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