Clinical trial NCT05632380: ASCT in Combination With C-CAR088 for Treating Patients With Ultra High-risk Multiple Myeloma (MM)
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
Collaborators: name: Shanghai AbelZeta Ltd.
First posted: 2022-11-30
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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 0-1.
* 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

Primary outcomes:
measure: Incidence rate and severity of adverse events (AE)
timeFrame: 24 months
Secondary outcomes:
measure: Progression free survival (PFS)
timeFrame: 24 months
measure: MRD negativity rate
timeFrame: 24 months
measure: Overall response rate (ORR)
timeFrame: 24 months
measure: Duration of response (DOR)
timeFrame: 24 months
measure: Time to response (TTR)
timeFrame: 24 months
measure: Overall Survival (OS)
timeFrame: 24 months
measure: Cmax (maximal plasma concentration)
timeFrame: 24 months
measure: Tmax (Time to reach the maximal plasma conceration)
timeFrame: 24 months
measure: AUC0-28d (area under the curve from day 0-day 28)
timeFrame: 28 days post C-CAR088 infusion
measure: Tlast (Time of last measurable observed concentration)
timeFrame: 24 months
Other outcomes:
measure: Anti-drug (C-CAR088) antibody
timeFrame: 24 months
Locations:
city: Tianjin
country: China
facility: Institute of Hematology & Blood Diseases Hospital
state: Tianjin
Study officials:
affiliation: Institute of Hematology & Blood Diseases Hospital, China
name: Dehui Zou, M.D., PH.D.
role: PRINCIPAL_INVESTIGATOR
References: