A Study of CAR-T Cells Targeting Both BCMA and GPRC5D in Treatment of Relapsed or Refractory Multiple Myeloma

An Open-Label, Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of BMCA and GPRC5D Dual Target CAR-T Cells Therapy in Patients With Relapsed or Refractory Multiple Myeloma

An Open-Label, Dose Finding Study to Investigate the Safety, Pharmacokinetics, and Preliminary Efficacy of BMCA and GPRC5D dual target CAR-T cells therapy in Patients with relapsed or refractory multiple myeloma

Study Overview

• Status: Not yet recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Biological: BMCA and GPRC5D dual target CAR-T cells(OriC321)

• Study Type: Interventional
• Enrollment (Anticipated): 9
• Phase: Phase 1

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:

• Signed and dated, written informed consent prior to any study specific procedures;
• Estimated life expectancy of minimum of 12 weeks;
• ECOG 0-2;
• Diagnosed as multiple myeloma according to the IMWG criteria;

• Evidence of cell membrane GPRC5D and/or BCMA expression, as determined by a validated immunohistochemistry (IHC) or flow cytometry of tumor tissue; Subjects should have measurable disease. At least meet one of the following criteria:

  1. If IgG type MM, serum M protein ≥10g/L; if IgA, IgD, IgE or IgM type MM, serum M protein ≥5g/L;
  2. urine M protein level ≥0.2g(200mg/24h);
  3. light chain type MM, serum free light chain (sFLC) ≥ 100mg / L and K/ λ FLC ratio is abnormal;
  4. there are extramedullary lesions;
• Subjects have had at least 3 prior lines of therapy including chemotherapy based on proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs);
• Adequate organ functions

Exclusion Criteria:

• Active smoldering multiple myeloma;
• Active plasma cell leukemia;
• With organ amyloidosis;
• Central nervous system (CNS) involvement;
• Pregnant or breastfeeding;
• Hepatitis B virus (HBV) surface antigen (HBsAg) or hepatitis B core antibody-positive and detectable HBV DNA in peripheral blood; Hepatitis C virus (HCV) antibody and hepatitis C virus RNA in peripheral blood; Human immunodeficiency virus (HIV) antibody
• Uncontrolled Hypertension hypertension defined as a blood pressure (BP) ≥150/95 mmHg; Symptomatic heart failure per New York Heart Association Classification Class II, III or IV), Mean resting corrected QT interval corrected by Fridericia's formula (QTcF) > 470 msec (female), 450 msec (male) obtained from ECG; Baseline left ventricular ejection fraction (LVEF) below institution's lower limit of normal (LLN) or <50%;
• Have a history of another primary malignancy within 5 years prior to starting study treatment. Exceptions here are as follows: the disease under study; adequately treated basal or squamous cell carcinoma of the skin; cancer of the cervix in situ.

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: BMCA and GPRC5D dual target CAR-T cells （OriC321）	Biological: BMCA and GPRC5D dual target CAR-T cells(OriC321); Patients will receive lymphodepleting chemotherapy followed by a single infusion of OriC321

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence, severity AEs/SAEs	2 years after CAR-T cell infusion

Secondary Outcome Measures

Outcome Measure	Time Frame
Concentration of CAR-T cells	2 years after CAR-T cell infusion
Objective response rate (ORR)	2 years after CAR-T cell infusion
Progression-free survival (PFS)	2 years after CAR-T cell infusion
Duration of response (DOR)	2 years after CAR-T cell infusion
Overall survival (OS)	2 years after CAR-T cell infusion
Percentage of Patients With Negative Minimal Residual Disease (MRD)	2 years after CAR-T cell infusion

Collaborators and Investigators

• Sponsor: Zhejiang University

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2022
• Primary Completion (Anticipated): March 1, 2024
• Study Completion (Anticipated): March 1, 2025

Study Registration Dates

• First Submitted: March 15, 2022
• First Submitted That Met QC Criteria: April 5, 2022
• First Posted (Actual): April 13, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

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: SIRIUS

Drug and device information, study documents

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