Clinical trial NCT05521802: A Study of C-CAR088 in Patients With Relapsed or Refractory Multiple Myeloma
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Shanghai AbelZeta Ltd.
Sponsor class: INDUSTRY
First posted: 2022-08-30
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: [phase Ib] Incidence and severity of Adverse Events
timeFrame: 24 months
measure: [phase II] Overall response rate (ORR) at 3 months after C-CAR088 infusion
timeFrame: 3 months
Secondary outcomes:
measure: Overall response rate (ORR)
timeFrame: 24 months
measure: [phase Ib] Overall response rate (ORR) at 3 months after C-CAR088 infusion
timeFrame: 3 months
measure: Duration of response (DOR)
timeFrame: 24 months
measure: Time to response (TTR)
timeFrame: 24 months
measure: Progression-free survival (PFS)
timeFrame: 24 months
measure: Overall survival (OS)
timeFrame: 24 months
measure: Minimal residual disease (MRD) negativity rate
timeFrame: 24 months
measure: [phase II] Incidence and severity of Adverse Events
timeFrame: 24 months
measure: Maximal plasma concentration (Cmax)
timeFrame: 24 months
measure: Time to reach the maximal plasma concentration (Tmax)
timeFrame: 24 months
measure: Area under the curve within 28 days (AUC0-28d)
timeFrame: 28 days
measure: Time of last measurable observed concentration (Tlast)
timeFrame: 24 months
measure: Anti-drug (C-CAR088) antibody
timeFrame: 24 months
measure: Serum M protein
timeFrame: 24 months
measure: Urine M protein
timeFrame: 24 months
measure: Serum free light chain (sFLC)
timeFrame: 24 months
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Institute of Hematology and Blood Diseases Hospital
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Lugui Qiu
role: PRINCIPAL_INVESTIGATOR
References: