A Study of C-CAR088 in Patients With Relapsed or Refractory Multiple Myeloma

A Phase Ib/II Study of CBM.BCMA Chimeric Antigen Receptor T Cell Product (C-CAR088) for Treating Patients With Relapsed or Refractory Multiple Myeloma

This is a multicenter, open-label study to evaluate the safety and efficacy of C-CAR088 in patients with relapsed or refractory multiple myeloma. The phase Ib part of this study is to determine the recommended phase 2 dose (RP2D) of C-CAR088 in the targeted patient population.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: B-cell maturation antigen (BCMA) directed chimeric antigen receptor (CAR)-T cell

Detailed Description

The study includes the following sequential procedures: Screening, Apheresis and C-CAR088 manufacturing, Baseline testing, Lymphodepletion, C-CAR088 infusion, and Follow-up Visit. Two dose levels of C-CAR088 will be tested during the phase Ib part to determine RP2D, which will be further evaluated during the phase II part.

• Study Type: Interventional
• Enrollment (Anticipated): 92
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Tianjin, China
    • Recruiting
    • Institute of Hematology and Blood Diseases Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

• ≥ 18 years of age, male or female patients
• Relapsed or refractory multiple myeloma
• Have been treated with ≥ 3 prior lines of therapy, including at least one proteasome inhibitor and one immunomodulatory drug, and had progressed during or within 12 months post the last treatment.

• Had measurable disease as defined by any of the following criteria:

  • Serum M protein ≥ 0.5g/dL
  • Urine M protein ≥ 200mg/24h
  • Serum free light chain (sFLC): abnormal κ/λ ratio with involved sFLC ≥ 100mg/L
• Adequate liver, renal, bone marrow, and heart function
• Eastern cooperative oncology group (ECOG) 0-1

Exclusion Criteria

• Any known allergies to the components or excipients of the C-CAR088 cell product
• Prior allogeneic hematopoietic stem cell transplantation (HSCT) at anytime, or autologous stem-cell transplantation (ASCT) within 12 weeks prior to apheresis
• Central nervous system (CNS) involvement
• Stroke or convulsion history within 6 months prior to signing informed consent form (ICF)
• Plasma leukemia
• Autoimmune disease, immunodeficiency or diseases requiring immunosuppressants treatment
• Uncontrolled active infection; active hepatitis B virus (HBV), hepatitis C virus (HCV) infection; HIV or syphilis infection
• Severe heart, liver, renal or metabolism disease
• Inadequate wash-out time for previous anti-tumor treatments prior to apheresis
• Previous CAR-T cell treatment, genetically modified T-cell therapies or BCMA-directed treatment history
• History or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in 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; Autologous C-CAR088 administered by intravenous (IV) infusion	Biological: B-cell maturation antigen (BCMA) directed chimeric antigen receptor (CAR)-T cell; Autologous 2nd generation BCMA-directed CAR-T cells, single infusion intravenously

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
[phase Ib] Incidence and severity of Adverse Events	Incidence and severity of Adverse Events	24 months
[phase II] Overall response rate (ORR) at 3 months after C-CAR088 infusion	the rate of patients with best response of partial response (PR) or better at 3 months after C-CAR088 infusion	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR)	The rate of patients with best response of partial response (PR) or better	24 months
[phase Ib] Overall response rate (ORR) at 3 months after C-CAR088 infusion	The rate of patients with best response of partial response (PR) or better at 3 months after C-CAR088 infusion	3 months
Duration of response (DOR)	The time from the first documented PR or better response to relapse or death, whichever occurs first	24 months
Time to response (TTR)	The time from the date of C-CAR088 infusion to the first documented PR or better	24 months
Progression-free survival (PFS)	The time from the date of C-CAR088 infusion to the date of first documented disease progression or death	24 months
Overall survival (OS)	The time from the date of C-CAR088 infusion to the date of death	24 months
Minimal residual disease (MRD) negativity rate	The rate of patients reached MRD negativity	24 months
[phase II] Incidence and severity of Adverse Events	Incidence and severity of Adverse Events	24 months
Maximal plasma concentration (Cmax)	maximal plasma concentration of C-CAR088 in peripheral blood	24 months
Time to reach the maximal plasma concentration (Tmax)	Time to reach the maximal plasma concentration of C-CAR088 in peripheral blood	24 months
Area under the curve within 28 days (AUC0-28d)	Area under the curve of C-CAR088 in peripheral blood within 28 days post infusion	28 days
Time of last measurable observed concentration (Tlast)	Time of last measurable observed concentration of C-CAR088 in peripheral blood	24 months
Serum M protein	serum M proteins concentration changes over time	24 months
Urine M protein	Urine M proteins concentration changes over time	24 months
Serum free light chain (sFLC)	Serum free light chain (sFLC) concentration changes over time	24 months
Anti-drug (C-CAR088) antibody	Presence of serum anti-drug (C-CAR088) antibody	24 months

Collaborators and Investigators

• Sponsor: Cellular Biomedicine Group Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2022
• Primary Completion (Anticipated): July 1, 2024
• Study Completion (Anticipated): July 1, 2037

Study Registration Dates

• First Submitted: August 28, 2022
• First Submitted That Met QC Criteria: August 28, 2022
• First Posted (Actual): August 30, 2022

Study Record Updates

• Last Update Posted (Actual): March 24, 2023
• Last Update Submitted That Met QC Criteria: March 22, 2023
• Last Verified: March 1, 2023

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: 0203-029

Drug and device information, study documents

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