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 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): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Peihua Lu, PhD&MD; Phone Number: +86-0316-3306393; Email: Peihua_lu@126.com

Study Locations

• China
  • Hebei
    • Sanhe, Hebei, China, 065200
      • Recruiting
      • Hebei yanda Ludaopei Hospital
      • Contact: Peihua Lu, PhD&MD; Phone Number: +86-0316-3306393

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 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 18-70 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 who meet at least one of the following conditions:

   • Subjects must have received at least two therapy regimens (including proteasome inhibitor or immune-modulator therapy, disease progress or relapse after the last therapy).
   • Subjects have received only one therapy regimen, but the investigators judge that patients have unmet treatment needs or can't get benefit from current treatment options.

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 following 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 CNS metastasis or symptoms of CNS involvement.
8. The investigators judge that any increase in the risk of the subject or interference with the results of the trial.
9. After allogeneic hematopoietic stem cell transplantation.
10. Plasma cell leukemia.
11. One week before leukapheresis and one week before CART cell infusion, treated with more than 5mg/d prednisone (or equal amount of other corticosteroids).
12. Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy.
13. Uncontrolled active infection.
14. Prior treatment with CAR T therapy or any other genetically modified T cell therapy.
15. Live vaccine inoculation within four weeks before enrollment.
16. 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.
17. Have a history of alcoholism, drug addiction and mental illness.
18. Participated in any other clinical trial within three months.
19. 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, single infusion intravenously at a target dose of 1.0-9.0 x 10^6 anti-BCMA CAR+ T cells/kg; Other Names: CBM.BCMA Chimeric Antigen Receptor T cell

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)		12 months
Progression free survival (PFS)		6 months, 12 months
The CART cell duration in vivo	The copys of BCMA-CART DNA in peripheral blood with qPCR method	12 months
The soluble BCMA changes in peripheral blood	The amount of soluble BCMA in peripheral blood with ELISA method	12 months

Collaborators and Investigators

• Sponsor: Hebei Yanda Ludaopei Hospital

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): January 8, 2019
• Primary Completion (Anticipated): October 30, 2019
• Study Completion (Anticipated): October 30, 2020

Study Registration Dates

• First Submitted: November 15, 2018
• First Submitted That Met QC Criteria: November 20, 2018
• First Posted (Actual): November 23, 2018

Study Record Updates

• Last Update Posted (Actual): May 15, 2019
• Last Update Submitted That Met QC Criteria: May 13, 2019
• Last Verified: May 1, 2019

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: 0203-006

Drug and device information, study documents

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