Clinical trial NCT05325801: A Study of CAR-T Cells Targeting Both BCMA and GPRC5D in Treatment of Relapsed or Refractory Multiple Myeloma
Official title: 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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Multiple Myeloma
Lead sponsor: Zhejiang University
Sponsor class: OTHER
First posted: 2022-04-13
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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


Eligibility criteria: 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.

Primary outcomes:
measure: Incidence, severity AEs/SAEs
timeFrame: 2 years after CAR-T cell infusion
Secondary outcomes:
measure: Concentration of CAR-T cells
timeFrame: 2 years after CAR-T cell infusion
measure: Objective response rate (ORR)
timeFrame: 2 years after CAR-T cell infusion
measure: Progression-free survival (PFS)
timeFrame: 2 years after CAR-T cell infusion
measure: Duration of response (DOR)
timeFrame: 2 years after CAR-T cell infusion
measure: Overall survival (OS)
timeFrame: 2 years after CAR-T cell infusion
measure: Percentage of Patients With Negative Minimal Residual Disease (MRD)
timeFrame: 2 years after CAR-T cell infusion
Other outcomes:
Locations:
Study officials:
References: