Multiple Myeloma
Conditions
Brief summary
This is a single-arm, non-randomized, open-label study to confirm the RP2D (recommended phase 2 dose) of GC012F injection in patients with Relapsed/Refractory multiple myeloma (RRMM).
Detailed description
This is a single-arm, non-randomized, open-label study to evaluate the RP2D of GC012F injection in patients with Relapsed/Refractory multiple myeloma (RRMM). Approximately 6-9 eligible patients will be enrolled in escalating dosing cohorts to evaluate the RP2D of GC012F injection. Pts will be enrolled concurrently and assessed for ORR and DLT in respective dosing cohort. Based on this assessment the RP2D will be confirmed. Table1 Dose Level Dose Level DL-1 DL1 DL2 Dose 1×105 /kg 2×105 /kg 3×105 /kg Patients who signed the informed consent will be screened for inclusion/exclusion criteria, and 3 eligible subjects will be enrolled in DL1. 1. After the DLT observation period of 21 days, if ≤1 of the first 3 subjects has a DLT event, 3 additional subjects will be enrolled in DL1. \- ORR will be assessed at prespecified timepoints up to 24-weeks post treatment. A. If ORR \> 66%, the study concludes and respective dose level will be determined as RP2D B. If ORR≤66%, 3 subjects will be enrolled in DL2 2. If \> 1 of the 3 enrolled subjects has a DLT event, 3 more subjects will be enrolled in the lower dose level 2\. During the DLT observation period, if \> 1 of the first 3 subjects has a DLT event, 3 subjects will be enrolled in DL-1 to evaluate safety. Patients in each dose group will be closely observed for at least 21 days post GCO12F infusion for DLT. Safety and DLT will be assessed by SMC according to definition of protocol for DLT. There will be no fixed dose interval between each dose level and each patient within the dose cohort. In addition, after one year of infusion, patients will be rolled over to a protocol for long-term safety to assess risk of RCL and lentivirus insert in vivo. This study will be divided into six parts: screening, apheresis, baseline assessment, lymphodeleption, CAR-T cell infusion, and follow-up. Eligible patients will be apheresed and infused after CAR-T product release, patients will receive a 3-days standard F/C chemotherapy regimen for lymphodeleption. The recommend regimens for chemotherpay are as follows FC regimen: 1. Fludarabine 30 mg/m2/d, iv gtt for 3 days; 2. Cyclophosphamide 300 mg/m2/d, iv for 3 days. GC012F infusion will be performed at 48-72 hours after chemotherapy pretreatment. After GC012F infusion, subjects will be followed for safety and efficacy up to 1 year, or disease progression, death or withdrawal whichever comes earlier. In case of progression of disease,subsequent survival follow-up (survival state only) will be performed every 84 days (12 weeks) ± 14 days (2 weeks) till death,loss of follow up, or withdraw of consent. If there is no disease progression after 1 year of infusion, the same follow-up for survival will be carried out as mentioned above. End of this study will be 1 year after the last patient received infusion with GC012F. All patients who complete the study, as well as those who discontinue from the study after receiving GC012F for reasons other than death, will be asked to participate in a 15 years follow-up study to monitor RCL and lentivirus insert sites in vivo.
Interventions
BIOLOGICALGC012F injection
GC012F injection is a autologous dual CAR-T targeted BCMA and CD19. A single infusion of CART cells will be administered intravenously.
Sponsors
Gracell Biotechnologies (Shanghai) Co., Ltd.
Shanghai Changzheng Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Eligible patients should meet all the following criteria: 1. Age of 18-70 years at the time of signing informed consent (contains critical values)； 2. Documented diagnosis at initial of active multiple myeloma according to IMWG criteria, and meet one or more of the following criteria at screening: 1. Serum M protein ≥ 1 g/dL 2. Urine M protein ≥ 200 mg/24h 3. Serum free light chain sFLC ≥ 10 mg/dL with abnormal serum κ/λ ratio 3. Have had at least 3 different prior lines of therapy or primary refractory and PD within 12 months of their last line of therapy (patient should undergo at least 1 complete cycle of treatment in each line of therapy) defined by Consensus recommendations for the uniform reporting of clinical trials: report of the International Myeloma Workshop Consensus Panel 1; or patients have had at least 2 different prior lines of therapy and refractory to both IMiD and PI; 4. Estimated life expectancy ≥3 months; 5. ECOG: 0 or 1; 6. Hemoglobin ≥ 7.0 g/dL (without prior RBC transfusion within 7 days before screening; recombinant human erythropoietin use is permitted); 7. Absolute neutrophil count ≥ 1×109/L (without recombinant human granulocyte colony-stimulating factor within 7 days before screening and without pegylated G-CSF within 14 days of the laboratory test); 8. Platelet count ≥50×109/L(without prior platelet transfusion within 7 days before the laboratory test) 9. Absolute lymphocyte count ≥ 0.1×109/L; 10. Adequate functional reserve of organs: 1. ALT/AST ≤ 2.5× UNL (upper normal limit); 2. Serum creatinine \> 45 mL/min, calculated by Cockcroft-Gault; 3. Serum total bilirubin ≤ 2× UNL, except in subjects with congenital bilirubinemia (for participants with Gilbert syndrome, direct bilirubin ≤ 1.5× UNL is required); 4. Calibrated serum calcium ≤ 12.5 mg/dL (≤ 3.1 mmol/L) or free ionized calcium ≤ 6.5 mg/dL (≤ 1.6 mmol/L); 11. Sufficient venous access for leukapheresis collection, and no other contraindications to leukapheresis; 12. Woman of childbearing age must have serum HCG negative during screen and baseline. Males agreed to avoid sperm donation at least 1 year after GC012F infusion. Males and sexual partner with fertility are willing to use effective and reliable method of contraception for at least 1 year after infusion; 13. Ability and willingness to adhere to the study visit schedule and all protocol requirements; 14. Subjects themselves or their legal representatives must voluntarily sign written informed consent form(s).
Exclusion criteria
• Patients should be excluded if they meet any one of the following criteria:
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dose limitinged toxicity（DLT）after GC012F infusion | Up to 21 days after patients infused with GC012F injectiom | Incidence of dose-limiting toxicities within 21 days after GC012F infusion. |
| Adverse Events (AE) after infusion | Up to 48 weeks after patients infused with GC012F injectiom | Incidence of adverse events within 48 weeks after GC012F infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate(ORR) | Up to 24 weeks after patients infused with GC012F injectiom | Response assessed according to IMWG criteria (Kumar, Shaji et al. 2016), ORR (sCR, CR,VGPR, and PR) within 24 weeks after infusion Minimal Residual Disease (MRD) assessed by Euroflow ; |
| Progression-free survival (PFS), Overall Survival (OS), Duration Of Response (DOR) | Up to 1/3/6/9/12 months after patients infused with GC012F injectiom | Progression-free survival (PFS), overall survival (OS), duration of response (DOR) within 48 weeks after infusion (1/3/6/9/12 months after infusion); |
| CAR-T cell counts and number of CAR gene copies | Up to 48 weeks after patients infused with GC012F injectiom | CAR-T cell counts and number of CAR gene copies in the blood, bone marrow and/or tumor tissue within 48 weeks after GC012F infusion. |
Countries
China
Contacts
Primary ContactJuan Du, MD
Outcome results
None listed