This is a single-arm, single-center, open-label clinical study to evaluate the safety and efficacy of GC012F in high-risk, transplant eligible patients with NDMM.
Twenty evaluable subjects are planned to be enrolled in this study. Apheresis will be carried out in subjects who meet eligible criteria, and total 2 cycles of induction therapy (three-drug combination regimen based on bortezomib with details determined by the investigator according to the patient's condition) will be selectively given to subjects before or after apheresis. Next, subjects will receive a single infusion of GC012F, and the efficacy assessments will be performed at 1 month, 3 months, and every 3 months within 2 years until the end of the trial (MRD testing is required for each efficacy assessment), 1.Efficacy assessments performed at the 1st and 3rd months after infusion: 1. \<PR: Protocol change or transplantation or follow-up decided by the investigator. 2. ≥PR: MRD positive: Protocol change or transplantation or follow-up decided by the investigator. MRD negative: Wait for next follow-up. 2.Efficacy assessments performed at the 6th month after infusion and every 3 months thereafter: 1. MRD positive: Protocol change or transplantation or follow-up decided by the investigator. 2. MRD negative: Whether to carry out maintenance treatment using lenalidomide until the end of the trial will be determined by the investigator. After signing the informed consent form (ICF), subjects will be followed up for efficacy and safety until 2 years after GC012F infusion, or disease progression, or death, or withdrawal of consent, or any intolerable toxicity, whichever comes first. All AEs in subjects, especially infection related symptoms and signs, will be closely monitored during follow-up, and prophylactic treatment will be administered according to clinical practice when necessary. In case of disease progression within 2 years after GC012F infusion, treatment will be administered according to clinical practice, and the survival follow-up (only for the survival status) will be performed every 12 weeks±14 days (2 weeks) until 2 years after infusion, or death, or withdrawal of consent, whichever comes first. For subjects who have undergone transportation or any other clinical routine treatments after GC012F infusion, survival follow-up will be also performed as described above.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
GC012F injection is an autologous dual CAR-T targeted BCMA and CD19. A single infusion of CAR-T cells will be administered intravenously.
Shanghai Changzheng Hospital
Shanghai, Shanghai Municipality, China
RECRUITINGAdverse Events (AE) after GC012F infusion
An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), with the exception of cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS). CRS and ICANS should be evaluated according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading
Time frame: Up to 1 year after patients infused with GC012F injection
Overall response rate (ORR) as measured by International Myeloma Working Group (IMWG) criteria after GC012F infusion
ORR defined as proportion of patients achieving PR or better based on IMWG defined response criteria
Time frame: Up to 2 years after patients infused with GC012F injection
Percentage of patients with minimal residual disease (MRD) negative(tested by NGF at sensitivity of 10e-5 to 10e-4) at landmark analysis of 1/3/6/12/18/24 months post GC012F infusion
MRD negative rate is defined as the proportion of participants who achieve MRD negative status by the respective time point
Time frame: Up to 2 years after patients infused with GC012F injection
Progress free survival (PFS) at 6 months, 12 months and 24 months after GC012F infusion
PFS defined as time from date of GC012F infusion to date of first documented disease progression, or death due to any cause, whichever occurs first. DOR defined as time form Month 1 after GC012F infusion to date of 1st documented PD if patients' response deeper or keeping sCR after CAR-T infusion.
Time frame: Up to 2 years after patients infused with GC012F injection
Duration of response (DOR) at 6 months, 12 months and 24 months after GC012F infusion
DOR defined as time form Month 1 after GC012F infusion to date of 1st documented PD if patients' response deeper or keeping sCR after CAR-T infusion.
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Time frame: Up to 2 years after patients infused with GC012F injection
Overall survival (OS) after GC012F infusion
Response is defined as participant has met all criteria for PR or better according to IMWG criteria
Time frame: Up to 2 years after patients infused with GC012F injection
Time to first response (TTR) after GC012F infusion
Response is defined as participant has met all criteria for PR or better according to IMWG criteria
Time frame: Up to 2 years after patients infused with GC012F injection
Time to best response (TBR) after GC012F infusion
Response is defined as participant has met all criteria for PR or better according to IMWG criteria
Time frame: Up to 2 years after patients infused with GC012F injection
Change from Baseline in Health-related Quality of Life (HRQoL) as Measured by EORTC QLQ-C30
HRQoL will be assessed by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core-30 (QLQC30) items. Subscale and single item scores are reported on a 0-100 scale with higher scores representing better global health status, better functioning, and worst symptoms.
Time frame: Baseline up to study completion ( 2 years after GC012F Infusion on Day 0
Change from Baseline in HRQoL as Measured by EORTC QLQ-MY20
HRQoL will be assessed by the EORTC QLQ-Multiple Myeloma ((MY20) module items. Subscale and single item scores are reported on a 0-100 scale with higher scores representing better global health status, better functioning, and worst symptoms.
Time frame: Baseline up to study completion ( 2 years after GC012F Infusion on Day 0
Change from Baseline in Participant-reported Health Status Measured by EQ-5D- 5L
Participant-reported health status measured by the EuroQol Group 5-dimension, 5-level (EQ-5D-5L) questionnaire. A total utility score is reported based on the health status, ranging from 0 to 1, where higher values indicate better health utility. The visual analog scale ranges from 0 to 100 where higher values indicate better overall health status.
Time frame: Baseline up to study completion ( 2 years after GC012F Infusion on Day 0
Change from Baseline in Pain Measured by PGIS Scale [Time Frame: Baseline up to study completion
Participant reported pain measured by Patient Global Impression of Severity (PGIS) Scale. The PGIS is a single item to assess pain severity. The 5-point verbal rating scale ranged from 1 (none) to 5 (very severe).
Time frame: Baseline up to study completion ( 2 years after GC012F Infusion on Day 0
Level of CAR-T Cell Expansion (proliferation), and Persistence
Levels of GC012F cell expansion (proliferation), and persistence via monitoring CAR-T positive cell counts and CAR transgene level will be reported.
Time frame: Up to 2 years after patients infused with GC012F injection
Cytokines in the peripheral blood after GC012F infusion
Serum concentrations of Granulocyte-macrophage Colony Stimulating Factor (GM-CSF), interleukin (IL)-6, IL-10, interferon-gamma (IFN-γ), soluble BCMA (sBCMA) and TNF-α after GC012F infusion
Time frame: Up to 2 years after patients infused with GC012F injection
Serum concentrations of C-reaction protein (CRP)
Serum concentrations of C-reaction protein (CRP)
Time frame: Up to 2 years after patients infused with GC012F injection
Number of patients with Anti-GC012F Antibodies, replication-competent lentivirus (RCL) after GC012F infusion
Number of patients exhibiting anti-drug antibodies for GC012F and RCL will be reported
Time frame: Up to 2 years after patients infused with GC012F injection