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

A Phase # 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 patients.

Study Overview

• Status: Unknown
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: C-CAR088

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lu Zhang; Phone Number: 010-69155660; Email: pumczhanglu@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Peking Union Medical College Hospital
      • Contact: Lu Zhang; Phone Number: 010-69155660; Email: pumczhanglu@163.com

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. Age 18-75 years old, male or female;
2. The patient volunteered to participate in the study, and he or his legal guardian signed the Informed Consent;
3. Patients with a clear diagnosis of relapsed or refractory multiple myeloma

4. The patient have one or more measurable multiple myeloma lesion, must include one of the following conditions:

   • Serum M protein≥1.0 g/dL(10g/L)
   • Urine M protein≥200 mg/24h
   • Serum free light chain(sFLC): κ/λ FLC ratio is abnormal and affected FLC ≥10mg / dL
5. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination;
6. At least 2 weeks from monoclonal antibody therapy prior to CAR T cell therapy.
7. ECOG scores 0 - 1;
8. Good cardiac and pulmonary organ function;
9. Expected survival time > 12 weeks;.
10. Female subjects of childbearing age must have a negative urine / blood pregnancy test within 7 days before cell therapy and not be in lactation; female or male subjects of childbearing age need to take effective contraception throughout the study.

Exclusion Criteria:

1. Have a history of allergy to cellular products;
2. Laboratory testing occurs when: including but not limited to, serum total bilirubin ≥1.5mg / dl; serum ALT or AST is 2.5 times higher than the upper limit of normal value; serum creatinine ≥2.0mg / dl; hemoglobin <80g / L; absolute neutrophil count <1000 / mm3 or dependent on GCSF or Other growth factors can maintain the centriole count ≥1000 / mm²; platelet count <50000 / mm³ or the above level can be maintained due to platelet transfusion;
3. Presence of clinically significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or any heart function Grade 3 (moderate) or Grade 4 (severe) heart disease (according to the New York Heart Association Function Classification method: NYHA); patients with a history of myocardial infarction, cardiac angioplasty or stent implantation, unstable angina pectoris or other clinically significant heart disease within 12 months before enrollment;
4. A history of craniocerebral trauma, consciousness disorder, epilepsy, severe cerebral ischemia or hemorrhagic disease;
5. Need to 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. After allogeneic hematopoietic stem cell transplantation;
9. Plasma cell leukemia;
10. Patients with autoimmune diseases, immunodeficiency, or other immunosuppressive agents;
11. Uncontrolled active infection;
12. Have used any CAR T cell products or other genetically modified T cell therapy before;
13. 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;
14. Have a history of alcoholism, drug addiction and mental illness;
15. Participated in any other clinical trial within 1 months;
16. 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	Drug: 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 Name: CBM.BCMA Chimeric Antigen Receptor T cell.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The Incidence of adverse events (TEAEs) within 30 days after intravenous infusion of C-CAR088	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	ORR(including sCR / CR / VGPR / PR, based on IMWG 2016 efficacy evaluation criteria)	12 months
Progression free survival (PFS)	PFS(based on IMWG 2016 efficacy evaluation criteria)	6 months#12 months

Collaborators and Investigators

• Sponsor: Peking Union Medical College Hospital
• Collaborators: Cellular Biomedicine Group Ltd.
• Investigators: Principal Investigator: Daobin Zhou, Peking Union Medical College 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): October 23, 2019
• Primary Completion (Anticipated): September 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: March 2, 2020
• First Submitted That Met QC Criteria: March 2, 2020
• First Posted (Actual): March 4, 2020

Study Record Updates

• Last Update Posted (Actual): March 4, 2020
• Last Update Submitted That Met QC Criteria: March 2, 2020
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Multiple Myeloma
• 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: 0203-007

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