A Study of BCMA-directed CAR-T Cells Treatment in Subjects With r/r Multiple Myeloma

A Phase Ⅰ Study Evaluating Safety and Efficacy of C-CAR088 Treatment in Subjects With Relapsed or Refractory Multiple Myeloma

This is a single-center, non-randomized and dose-escalation study to evaluate the safety and efficacy of C-CAR088 in relapsed or refractory multiple myeloma patient.

Study Overview

• Status: Unknown
• Conditions: Relapsed or Refractory Multiple Myeloma
• Intervention / Treatment: Biological: C-CAR088

Detailed Description

The study will include the following sequential phases: Screening, Pre- Treatment (Cell Product Preparation, Lymphodepleting Chemotherapy), C-CAR088 infusion and Follow-up.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 210000
      • Recruiting
      • The First Affiliated Hospital of Nanjing Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Volunteered to participate in this study and signed informed consent.
2. Age 18-75 years old, male or female.
3. Meet the internationally accepted Criteria for the diagnosis of multiple myeloma (IMWG diagnostic criteria 2014).
4. Patients with relapsed or refractory multiple myeloma.

5. Subjects have one or more measurable multiple myeloma lesion, must include one of the following conditions:

   • Serum M protein≥1 g/dl(10g/L)
   • Urine M protein≥200 mg/24h
   • Serum free light chain(sFLC): κ/λ ratio abnormal and ≥10 mg/dl
6. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.
7. At least 2 weeks from monoclonal antibody therapy prior to CAR T cell therapy.
8. ECOG scores 0 - 1.
9. Normal cardiac diastolic function, left ventricular ejection fraction (LVEF) ≥ 50% (detected by echocardiography), no serious arrhythmia.
10. No active pulmonary infections, normal pulmonary function and oxygen saturation ≥ 92% on room air.
11. No contraindications of leukapheresis.
12. Expected survival > 12 weeks.
13. Female subjects in childbearing age, their serum or urine pregnancy test must be negative,until 7 days before cell therapy and all subjects must agree to take effective contraceptive measures during the trial.

Exclusion Criteria:

1. Have a history of allergy to cellular products.
2. Any kind of these laboratory testing: including but not limited to,serum total bilirubin≧1.5mg/dl, serum ALT, AST≧2.5×ULN, serum creatinine≧2.0mg/dl, Hb (hemoglobin)<80g/L, neutrophils<1000/mm^3, platelets≦50000/mm^3 or platelet count maintained by transfusion.
3. Subjects with the clinically significant cardiovascular diseases.
4. A history of craniocerebral trauma, consciousness disorder, epilepsy, severe cerebral ischemia or hemorrhagic disease.
5. Use any anticoagulant (except aspirin).
6. Patients requiring urgent treatment due to tumor progression or spinal cord compression.
7. Patients with active CNS involvement or clinical syndrome of MM meningeal involvement.
8. After allogeneic hematopoietic stem cell transplantation.
9. Plasma cell leukemia.
10. Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy.
11. Uncontrolled active infection.
12. Prior treatment with CAR T therapy or any other genetically modified T cell therapy.
13. Live vaccine inoculation within four weeks before enrollment.
14. Hepatitis B or hepatitis C virus infection (including carriers), syphilis, as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons.
15. Have a history of alcoholism, drug addiction and mental illness.
16. Participated in any other clinical trial within one month.
17. The investigators believe that there are other circumstances that are not suitable for the trial.

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: C-CAR088; Lymphocytes will be transduced with lentiviral vector containing CAR-BCMA gene	Biological: C-CAR088; Autologous BCMA-directed CAR-T cells by a single infusion intravenously will be given in escalating doses.; Other Names: CBM.BCMA Chimeric Antigen Receptor T cell

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety:TEAEs	The incidence of treatment-emergent adverse events (TEAEs)	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall response rate	12 months
PFS	Progression free survival	6 months, 12 months

Collaborators and Investigators

• Sponsor: The First Affiliated Hospital with Nanjing Medical University

Publications and helpful links

General Publications

• Qu X, An G, Sui W, Wang T, Zhang X, Yang J, Zhang Y, Zhang L, Zhu D, Huang J, Zhu S, Yao X, Li J, Zheng C, Zhu K, Wei Y, Lv X, Lan L, Yao Y, Zhou D, Lu P, Qiu L, Li J. Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. J Immunother Cancer. 2022 Sep;10(9):e005145. doi: 10.1136/jitc-2022-005145.

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2019
• Primary Completion (Anticipated): January 1, 2021
• Study Completion (Anticipated): April 1, 2021

Study Registration Dates

• First Submitted: January 22, 2019
• First Submitted That Met QC Criteria: January 22, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): July 5, 2019
• Last Update Submitted That Met QC Criteria: July 1, 2019
• Last Verified: December 1, 2018

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: 0203-008

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No