The Safety and Efficacy of Autologous Hematopoietic Stem Cell Transplantation (ASCT) in Combination With C-CAR088, an Autologous BCMA CAR-T Cell Product, for Treating Patients With Ultra High-risk Multiple Myeloma
Overview
- Phase
- Phase 1
- Intervention
- Autologous hematopoietic stem cell transplantation
- Conditions
- Multiple Myeloma
- Sponsor
- Institute of Hematology & Blood Diseases Hospital, China
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Incidence rate and severity of adverse events (AE)
- Status
- Recruiting
- Last Updated
- 7 months ago
Overview
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.
Investigators
Eligibility Criteria
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-
- •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
Arms & Interventions
ASCT and C-CAR088
Patients will undergo ASCT followed by C-CAR088 single dose infusion.
Intervention: Autologous hematopoietic stem cell transplantation
ASCT and C-CAR088
Patients will undergo ASCT followed by C-CAR088 single dose infusion.
Intervention: C-CAR088
Outcomes
Primary Outcomes
Incidence rate and severity of adverse events (AE)
Time Frame: 24 months
Incidence rate and severity of adverse events (AE)
Secondary Outcomes
- AUC0-28d (area under the curve from day 0-day 28)(28 days post C-CAR088 infusion)
- MRD negativity rate(24 months)
- Progression free survival (PFS)(24 months)
- Duration of response (DOR)(24 months)
- Tmax (Time to reach the maximal plasma conceration)(24 months)
- Tlast (Time of last measurable observed concentration)(24 months)
- Time to response (TTR)(24 months)
- Overall response rate (ORR)(24 months)
- Overall Survival (OS)(24 months)
- Cmax (maximal plasma concentration)(24 months)