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

Primary Purpose

Multiple Myeloma

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
Autologous hematopoietic stem cell transplantation
C-CAR088
Sponsored by
Institute of Hematology & Blood Diseases Hospital, China
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Multiple Myeloma

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Institute of Hematology & Blood Diseases HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ASCT and C-CAR088

Arm Description

Patients will undergo ASCT followed by C-CAR088 single dose infusion.

Outcomes

Primary Outcome Measures

Incidence rate and severity of adverse events (AE)
Incidence rate and severity of adverse events (AE)

Secondary Outcome Measures

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

Full Information

First Posted
November 8, 2022
Last Updated
November 21, 2022
Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
Cellular Biomedicine Group Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT05632380
Brief Title
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

2. Study Status

Record Verification Date
November 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 14, 2022 (Actual)
Primary Completion Date
December 30, 2023 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Institute of Hematology & Blood Diseases Hospital, China
Collaborators
Cellular Biomedicine Group Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ASCT and C-CAR088
Arm Type
Experimental
Arm Description
Patients will undergo ASCT followed by C-CAR088 single dose infusion.
Intervention Type
Procedure
Intervention Name(s)
Autologous hematopoietic stem cell transplantation
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
C-CAR088
Intervention Description
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.
Primary Outcome Measure Information:
Title
Incidence rate and severity of adverse events (AE)
Description
Incidence rate and severity of adverse events (AE)
Time Frame
24 months
Secondary Outcome Measure Information:
Title
Progression free survival (PFS)
Description
The time from the initiation of study treatment to the date of first documented disease progression or death
Time Frame
24 months
Title
MRD negativity rate
Description
The percentage of patients who reached MRD negativity
Time Frame
24 months
Title
Overall response rate (ORR)
Description
The percentage of patients who reached PR, VGPR, CR or sCR as their best response
Time Frame
24 months
Title
Duration of response (DOR)
Description
The time from the first documented PR or better response to progression or death, whichever occurs first
Time Frame
24 months
Title
Time to response (TTR)
Description
The time between the initiation of study treatment until the the first documented PR or better response
Time Frame
24 months
Title
Overall Survival (OS)
Description
OS is defined as the time from the initiation of study treatment to death from any cause
Time Frame
24 months
Title
Cmax (maximal plasma concentration)
Description
Maximal plasma concentration of C-CAR088 in peripheral blood
Time Frame
24 months
Title
Tmax (Time to reach the maximal plasma conceration)
Description
Time to reach the maximal plasma conceration of C-CAR088 in peripheral blood
Time Frame
24 months
Title
AUC0-28d (area under the curve from day 0-day 28)
Description
Area under the curve of C-CAR088 in peripheral blood within 28 days post C-CAR088 infusion
Time Frame
28 days post C-CAR088 infusion
Title
Tlast (Time of last measurable observed concentration)
Description
Time of last measurable observed concentration of C-CAR088 in peripheral blood
Time Frame
24 months
Other Pre-specified Outcome Measures:
Title
Anti-drug (C-CAR088) antibody
Description
The correlation between the presence of anti-drug (C-CAR088) antibody with the efficacy and prognosis
Time Frame
24 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yan Xu, M.D., PH.D.
Phone
86-022-23909171
Email
xuyan1@ihcams.ac.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Dehui Zou, M.D., PH.D.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Dehui Zou, M.D., PH.D.
Organizational Affiliation
Institute of Hematology & Blood Diseases Hospital, China
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital
City
Tianjin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dehui Zou, M.D., Ph.D.
Phone
86-022-23909282
Email
zoudehui@ihcams.ac.cn

12. IPD Sharing Statement

Learn more about this trial

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

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