Study of Dual Targeted CD19/BCMA FASTCART GC012F in Relapsed/ Refractory Multiple Myeloma

Multiple Myeloma Clinical Trial

Official title: Open- Label Phase I Study to Assess the RP2D of GC012F CAR-T in Subjects With Relapsed/Refractory Multiple Myeloma

Status Recruiting

Clinical Trial 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).

Clinical Trial 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. ;

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

• NCT number: NCT05412329
• Study type: Interventional
• Source: Shanghai Changzheng Hospital
• Contact: Juan Du, MD
• Phone: +86-21-81885423
• Email: changzheng_pg@163.com
• Status: Recruiting
• Phase: Phase 1
• Start date: June 13, 2022
• Completion date: June 1, 2024