Safety and Efficacy of APRIL-BAFF-Bicephali CAR-T in Relapsed, Refractory Multiple Myeloma (CAR-T)

Safety and Efficacy of APRIL-BAFF-Bicephali CAR-T in Relapsed, Refractory Multiple Myeloma-A Single-center, Open-label, Single-arm Clinical Study

This is a Single-center, open, single-arm clinical study, the goal of which was to evaluate the safety and efficacy of APRIL-BAFF-Bicephali CAR-T in relapsed and refractory multiple myeloma.The study consisted of four processes: patient enrollment screening; pre-CAR T cell therapy (including leukocyte apheresis, CAR T cell preparation and chemotherapy); inpatient monitoring phase for CAR T cell transfusion; and long-term follow-up phase

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Other: APRIL-BAFF-Bicephali CAR-T cells

Detailed Description

This trial is a single-center, open, single-arm trial with a non-blinded design.

The study consisted of four processes: patient enrollment screening; pre-CAR T cell therapy (including leukocyte apheresis, CAR T cell preparation and chemotherapy); inpatient monitoring phase for CAR T cell transfusion; and long-term follow-up phase. The specific execution process is as follows:

1. Pre-enrollment assessment;
2. Patient enrollment and basic data collection;

3. Leukocyte apheresis and CAR-T cell production 3.1 Patients receive apheresis of about 12-15 liters to provide peripheral blood mononuclear cells for the preparation of CAR-T. In addition to the use of appropriate amounts of lymphocytes for CAR-T preparation, excess cells should be cryopreserved for subsequent studies and regulatory inquiries.

   3.2 APRIL-BAFF Bicephali CAR-T cell preparation. 4 cells were pretreated before transfusion Pretreatment was started-5 days before CAR-T cell revertant, and CAR-T cell treatment was performed 2 days after completion of chemotherapy. The purpose of chemotherapy is to reduce the tumor load on the one hand and to reduce the number of endogenous lymphocytes to facilitate the proliferation of reinfused CAR T cells. All patients were pretreated with FC regimen, fludarabine 30mg / m2 3days, cyclophosphamide 750mg / m2 1days. Antiemetic and symptomatic treatment could be given during chemotherapy, and generally treated with other chemotherapy.

4. Post-treatment assessment Subjects were assessed for toxicity as planned (weekly for 1 month, monthly for 6 months, and every 3 months thereafter); efficacy for every 4 weeks and every 3 months after 6 months. CAR-T cells were tested for in vivo expansion evaluation, including CD3 +, CD4 +, CD8 + T lymphocytes and B lymphocytes in peripheral blood.
5. purpose of research

1. Primary objective: To evaluate the effectiveness of APRIL-BAFF-Bicephali CAR-T in the treatment of relapsed and refractory multiple myeloma 2. Secondary objective: To evaluate its safety 3. Study design type, principles, and test procedures

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

Contacts and Locations

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

Study Locations

• China
  • Jiangsu
    • Xuzhou, Jiangsu, China, 221000
      • Recruiting
      • Kailin Xu
      • Contact: Kailin Xu, M.D., Ph.D.; 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:

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 co-stimulation (<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: Patients treated with CAR T cells; Peripheral blood mononuclear cells were collected and subjected to CD3+T cells were enriched, transfected with APRIL-BAFF-Bicephali lentiviral vector, expanded by in vitro culture, and pretreated with clear lymphocytes using the FC protocol before infusion of APRIL-BAFF-Bicephali CAR-T cells.	Other: APRIL-BAFF-Bicephali CAR-T cells; Peripheral blood mononuclear cells were collected and subjected to CD3+T cells were enriched, transfected with APRIL-BAFF-Bicephali lentiviral vector, expanded by in vitro culture, and pretreated with clear lymphocytes using the FC protocol before infusion of APRIL-BAFF-Bicephali CAR-T cells.

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
• Collaborators: Yake Biotechnology Ltd.
• Investigators: Study Chair: Kailin Xu MD, PD, The Affiliated Hospital oh Xuzhou Medical University

Study record dates

Study Major Dates

• Study Start (Actual): November 10, 2023
• Primary Completion (Estimated): January 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: July 11, 2023
• First Submitted That Met QC Criteria: November 14, 2023
• First Posted (Actual): November 15, 2023

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 14, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: myeloma, Chimeric antigen receptor, April, TACI
• 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-KL144-01

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