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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Procedure: Autologous hematopoietic stem cell transplantation; Biological: C-CAR088

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 Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yan Xu, M.D., PH.D.; Phone Number: 86-022-23909171; Email: xuyan1@ihcams.ac.cn
• Study Contact Backup: Name: Dehui Zou, M.D., PH.D.

Study Locations

• China
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Recruiting
      • Institute of Hematology & Blood Diseases Hospital
      • Contact: Dehui Zou, M.D., Ph.D.; Phone Number: 86-022-23909282; Email: zoudehui@ihcams.ac.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ASCT and C-CAR088; Patients will undergo ASCT followed by C-CAR088 single dose infusion.

Procedure: Autologous hematopoietic stem cell transplantation; 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.; Biological: C-CAR088; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-drug (C-CAR088) antibody	The correlation between the presence of anti-drug (C-CAR088) antibody with the efficacy and prognosis	24 months

Collaborators and Investigators

• Sponsor: Institute of Hematology & Blood Diseases Hospital
• Collaborators: Cellular Biomedicine Group Ltd.
• Investigators: Principal Investigator: Dehui Zou, M.D., PH.D., Institute of Hematology & Blood Diseases Hospital

Study record dates

Study Major Dates

• Study Start (Actual): July 14, 2022
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): June 30, 2025

Study Registration Dates

• First Submitted: November 8, 2022
• First Submitted That Met QC Criteria: November 21, 2022
• First Posted (Actual): November 30, 2022

Study Record Updates

• Last Update Posted (Actual): November 30, 2022
• Last Update Submitted That Met QC Criteria: November 21, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: 0203-037

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No