ASCT in Combination With C-CAR088 for Treating Patients With Ultra High-risk Multiple Myeloma (MM)

Phase 1

Recruiting

• Conditions: Multiple Myeloma
• Interventions: Procedure: Autologous hematopoietic stem cell transplantation; Biological: C-CAR088

• Registration Number: NCT05632380
• Lead Sponsor: Institute of Hematology & Blood Diseases Hospital, China

Brief Summary

This is a phase I/II, single-arm, open-lable study of autologous stem cell transplantation in combination with C-CAR088, an autologous BCMA CAR-T cell product, for patients with ulta high-risk multiple myeloma, defined as failed or unsatisfied responses to front line VRD-based treatment with or without the presence of multiple high-risk cytogenetic features.

Detailed Description

Patients with ultra high-risk multiple myeloma will undergo leukapheresis, stem cell mobilization and collection (could omit if collected before screening), conditioning, ASCT and C-CAR088 infusion. Patients receive a single dose of C-CAR088 three days post-ASCT. Two conditioning protocols and two dose levels of C-CAR088 will be used based on the investigator's discretion. Patients will be evaluated closely for safety of efficacy during the first three months, then less frequently in the following months until 24 months post-ASCT.

Study Timeline

• Study Start: 2022-07-14
• Status Verified: 2022-11
• Study First Submitted: 2022-11-08
• Study First Submitted QC: 2022-11-21
• Last Update Submitted: 2022-11-21
• Study First Posted: 2022-11-30
• Last Update Posted: 2022-11-30
• Primary Completion: 2023-12-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

• Transplantation eligible patients, male or female, aged 18 to 65 years
• Ultra high risk multiple myeloma, defined as failed or unsatisfied responses to front line VRD-based treatment with or without the presence of multiple high-risk cytogenetic features
• Adequate liver, renal, bone marrow, and heart function
• Eastern Cooperative Oncology Group (ECOG) Performance status 0-1.
• Male and female of reproductive potential must agree to use birth control during the study.

Exclusion Criteria

• Known allergies to the components or excipients of the C-CAR088 cell product
• Prior allogenic HSCT, or ASCT
• CNS involvement
• Stroke or convulsion history within 6 months prior to signing ICF
• Autoimmune disease, immunodeficiency or disease requiring immunosuppressants treatment
• Uncontrolled active infection; active HBV, HCV infection; HIV or syphilis Infection
• Severe heart, liver, renal or metabolism disease
• Inadequate wash-out time for previous anti-tumor treatments prior to apheresis
• Previous CAR-T cell treatment, genetically modified T-cell therapies or BCMA-directed treatment history
• History or current evidence of any condition, therapy, or laboratory abnormality that, in the opinion of the investigator, might confound the results of the trial, interfere with the patient's safe participation and compliance in the trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ASCT and C-CAR088	Autologous hematopoietic stem cell transplantation	Patients will undergo ASCT followed by C-CAR088 single dose infusion.
ASCT and C-CAR088	C-CAR088	Patients will undergo ASCT followed by C-CAR088 single dose infusion.

Primary Outcome Measures

Name	Time	Method
Incidence rate and severity of adverse events (AE)	24 months	Incidence rate and severity of adverse events (AE)

Secondary Outcome Measures

Name	Time	Method
AUC0-28d (area under the curve from day 0-day 28)	28 days post C-CAR088 infusion	Area under the curve of C-CAR088 in peripheral blood within 28 days post C-CAR088 infusion
MRD negativity rate	24 months	The percentage of patients who reached MRD negativity
Progression free survival (PFS)	24 months	The time from the initiation of study treatment to the date of first documented disease progression or death
Duration of response (DOR)	24 months	The time from the first documented PR or better response to progression or death, whichever occurs first
Tmax (Time to reach the maximal plasma conceration)	24 months	Time to reach the maximal plasma conceration of C-CAR088 in peripheral blood
Tlast (Time of last measurable observed concentration)	24 months	Time of last measurable observed concentration of C-CAR088 in peripheral blood
Time to response (TTR)	24 months	The time between the initiation of study treatment until the the first documented PR or better response
Overall response rate (ORR)	24 months	The percentage of patients who reached PR, VGPR, CR or sCR as their best response
Overall Survival (OS)	24 months	OS is defined as the time from the initiation of study treatment to death from any cause
Cmax (maximal plasma concentration)	24 months	Maximal plasma concentration of C-CAR088 in peripheral blood

Trial Locations

Locations (1)

Institute of Hematology & Blood Diseases Hospital; 🇨🇳 Tianjin, Tianjin, China