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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Procedure: Autologous hematopoietic stem cell transplantation
* Biological: C-CAR088


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASCT and C-CAR088<br>Patients will undergo ASCT followed by C-CAR088 single dose infusion. | Procedure: Autologous hematopoietic stem cell transplantation<br>* Patients receive transplantation conditioning followed by autologous hematopoietic stem cell transplantation after successful stem cell mobilization and collection. If previously collected stem cells are available, no stem cell mobilization or collection is required, and patients will receive conditioning directly.<br>Biological: C-CAR088<br>* C-CAR088 is an BCMA targeted Chimeric Antigen Receptor-T cell product. Patients will receive C-CAR088 single dose infusion 3 days after ASCT. The dose level of C-CAR088 will be determined by the investigator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate and severity of adverse events (AE) | Incidence rate and severity of adverse events (AE) | 24 months | 

Secondary Outcome Measures

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