a Study of CT0596 in Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Plasma Cell Leukemia

A Clinical Study to Explore the Safety, Efficacy, and Pharmacokinetics of CT0596 CAR-T Cell Injection in Patients With Relapsed/Refractory Multiple Myeloma and Relapsed/Refractory Plasma Cell Leukemia

This study is a single-arm, open-label, exploratory dose-escalation and dose-finding clinical trial to evaluate the safety, efficacy, cellular pharmacokinetics and pharmacodynamics of CT0596 cells in patients with R/R MM and PCL.RRMM and RRpPCL

Study Overview

• Status: Recruiting
• Conditions: Relapsed/Refractory Multiple Myeloma; Relapsed/Refractory Plasma Cell Leukemia
• Intervention / Treatment: Drug: CAR-T cells Infusion

Detailed Description

This study is a single-arm, open-label, exploratory dose-escalation and dose-finding clinical trial to evaluate the safety, efficacy, cellular pharmacokinetics and pharmacodynamics of CT0596 cells in patients with R/R MM and PCL.RRMM and RRpPCL.

During the trial, dose increases or decreases or dose expansion may be performed using i3+3 principle based on the safety and ,tolerability and PK data of the patients.

All Patients will undergo a DLT assessment period which is defined as the first 28 days starting from the day of CT0596 infusion. A patient is evaluable for DLTs if the patient received the planned CT0596 dose and either completed the 28 days of DLT evaluation period after CT0596 infusion or experienced a DLT. Enrolled patients who are not evaluable for DLTs during dose escalation may be replaced. Any Patients who are not DLT evaluable will still be followed for safety and efficacy per the SOA.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Juan Du, Ph D; Phone Number: 15800706091; Email: juan_du@live.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Shanghai Changzheng Hospital
      • Contact: Juan Du, PhD; Phone Number: 15800706091; Email: juan_du@live.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants must meet all of the following criteria to be enrolled:

1. Patients must voluntarily sign the informed consent form (ICF) and must be willing and be able to adhere to the trial visit schedule and other protocol requirements and agree to be in long term follow-up (LTFU) for up to 15 years as mandated by the regulatory guidelines.
2. Age ≥ 18 years;
3. Patients with R/RMM who have received at least 3 prior lines of therapy, including at least 1 proteasome inhibitor and at least 1 immunomodulator (IMiD). Patients with RRpPCL had received at least 1 prior line of therapy. Number of lines of therapy was defined according to the guidelines provided in Rajkuma[1]r 2015 . Patients must have received at least 1 complete cycle of therapy for each line of therapy.
4. According to multiple myeloma IMWG 2016 and plasma cell leukemia IMWG 2013, patients must have progressive disease following or during the last treatment.
5. Patients must have measurable disease based on at least one of the following parameters:
6. Expected survival > 12 weeks;
7. Eastern Cooperative Oncology Group (ECOG) score 0- 1 ;
8. Patients should meet the following test results
9. Female patients of childbearing potential must have a negative pregnancy test at screening and prior to receiving lymphodepletion therapy and are willing to use a highly effective and reliable method of contraception for 1 year after receiving study treatment and are absolutely prohibited from donating eggs for 1 year after receiving study treatment infusion during the study ;Male patients are willing to use a highly effective and reliable method of contraception for 1 year after receiving study treatment if they are sexually active with a female of childbearing potential. Sperm donation is absolutely prohibited within 1 year following study treatment infusion for all male patients during the study.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Patient has any significant condition(s), laboratory abnormality or psychiatric illness that would impair the ability of the patient to receive or tolerate the planned treatment or in the opinion of the investigator, participation would not be in the best interest of the patient (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments
3. Patients seropositive for HIV, active hepatitis C virus (HCV), or active hepatitis B virus (HBV) infection. History of treated hepatitis B or C is permitted if the viral load is undetectable per qPCR and or nucleic acid testing;
4. Patients with any uncontrolled active infection, including but not limited to patients with active tuberculosis (investigator 's judgment);
5. Toxicities caused by previous treatment have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) ≤ Grade 1, except alopecia and other events that are judged tolerable by the investigator;
6. Previous allogeneic stem cell transplantation; autologous stem cell transplantation within 12 weeks prior to signing informed consent;
7. Have received treatment for the disease within 14 days before informed consent
8. Have received cell therapy within 28 days before informed consent.
9. Systemic glucocorticoids equivalent to > 15 mg/day prednisone within 7 days prior to informed consent, with the exception of topical glucocorticoids;
10. Vaccination with live attenuated vaccines , inactivated vaccines or RNA vaccines within 4 weeks prior to informed consent;
11. Allergic or intolerant to lymphodepletion, tocilizumab, or allergic to components (DMSO) in CT0596 CART cell infusion preparation; or previous history of other serious allergies such as anaphylactic shock;
12. Patients Waldenström macroglobulinemia, POEMS syndrome, or primary light chain amyloidosis at Screening;
13. Patients with any of the following cardiac conditions within 6 months prior to screening:
14. Patients who require supplemental oxygen to maintain oxygen saturation > 92%; or Patients with known or suspected COPD who have Forced Expiratory Volume in 1 second (FEV1) < 50% of predicted normal on spirometry;
15. Patients with active autoimmune diseases, including but not limited to psoriasis, rheumatoid arthritis and other diseases requiring long-term immunosuppressive therapy;
16. Patients with second primary malignancies are not eligible if the second primary malignancy has required treatment within the past 2 years or is not in complete remission. Exceptions include the following that have been successfully treated - nonmetastatic basal cell or squamous cell skin carcinoma, non-metastatic prostate cancer, carcinoma-in-situ of breast or cervix, non-muscle invasive bladder cancer
17. Patients with symptomatic central nervous system (CNS) disease or suspected CNS metastases;
18. Major surgery within 2 weeks before informed consent or planned during the study period or within 4 weeks after giving study treatment (excluding local anesthesia such as cataract)

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: CAR-T cells Infusion; chimeric antigen receptor T cells	Drug: CAR-T cells Infusion; chimeric antigen receptor T cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AE) after CT0596 infusion	An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria	12 months after CT0596 infusion
MTD and/or dose range	Evaluate Dose limited toxicity and recommended dosage range after CT0596 infusion	12 months after CT0596 infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate (ORR) as assessed by the investigator	Overall response rate (ORR) defined as proportion of patients achieving partial response or better based on International Myeloma Working Group defined response criteria	12 months after CT0596 infusion
Complete response/stringent complete response (CR/sCR) rate	Rate of complete response/stringent complete response (CR/sCR) defined as proportion of patients achieving CR or better based on IMWG defined response criteria.	12 months after CT0596 infusion
Rate of very good partial response (VGPR) and above	Rate of complete very good partial response response/stringent complete response (VGPR/CR/sCR) defined as proportion of patients achieving VGPR or better based on IMWG defined response criteria	12 months after CT0596 infusion
Duration of response (DOR)	DOR is defined as the time from first achieving PR or better to confirmed disease progression or death from any cause	12 months after CT0596 infusion
Minimal residual disease (MRD) negative rate	Minimal residual disease (MRD) negative rate is defined as the proportion of patients with VGPR or better who achieved 10-5 sensitivity of nucleated cell	12 months after CT0596 infusion
Time to response (TTR)	TTR defined as the time from the date of apheresis to the date of initial assessment of PR or better according to IMWG2016 criteria	12 months after CT0596 infusion
Progression-free survival (PFS)	PFS defined as the time from the date of apheresis of the subject to the first assessment of confirmed disease progression or death from any cause according to IMWG2016 criteria, whichever occurs first.	12 months after CT0596 infusion
Peak value of CART cells	Time to peak expansion and peak expansion in plasma after infusion of CT0596 cells	12 months after CT0596 infusion
Overall survival (OS)	OS defined as the time from the date of apheresis of the subject to death from any cause	12 months after CT0596 infusion
Cytokines in the peripheral blood after CT0596 infusion	Serum concentrations of interleukin (IL)-6 after CT0596 infusion	12 months after CT0596 infusion
Area under the plasma concentration versus time curve (AUC) of CART cells	Area under the plasma concentration versus time curve (AUC) in plasma after infusion of CT0596 cells	12 months after CT0596 infusion
In vivo persistence of CART cells	CART cells duration in plasma after infusion of CT0596 cells	12 months after CT0596 infusion

Collaborators and Investigators

• Sponsor: Shanghai Changzheng Hospital
• Collaborators: CARsgen Therapeutics Co., Ltd.
• Investigators: Principal Investigator: Juan Du, Ph D, Shanghai Changzheng Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 11, 2024
• Primary Completion (Estimated): January 3, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 24, 2024
• First Submitted That Met QC Criteria: December 4, 2024
• First Posted (Actual): December 5, 2024

Study Record Updates

• Last Update Posted (Estimated): December 12, 2024
• Last Update Submitted That Met QC Criteria: December 11, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: CAR-T; Relapsed/Refractory Multiple Myeloma; Relapsed or Refractory Plasma Cell Leukemia
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Leukemia; Multiple Myeloma; Neoplasms, Plasma Cell; Leukemia, Plasma Cell
• Other Study ID Numbers: CT0596-CG6022_01

Drug and device information, study documents

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