Plasma Cell Leukemia
Conditions
Keywords
Plasma Cell Leukemia, CAR-T cells
Brief summary
This study is a single-arm, open-label, exploratory dose-escalation and dosefinding clinical trial to evaluate the safety, efficacy, cellular pharmacokinetics and pharmacodynamics of CT0596 cells in patients with PCL.
Detailed description
This study is a single-arm, open-label, exploratory dose-escalation and dosefinding clinical trial to evaluate the safety, efficacy, cellular pharmacokinetics and pharmacodynamics of CT0596 cells in patients with PCL. 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.
Interventions
CAR-T cells Infusion
Sponsors
CARsgen Therapeutics Co., Ltd.
Institute of Hematology & Blood Diseases Hospital, China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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. PCL after inductive treatment or R/R pPCL. 4. Patients must have measurable disease。 5. Expected survival \> 12 weeks; 6. Eastern Cooperative Oncology Group (ECOG) score 0- 1 ; 7. Patients should have good organ function。 8. 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. 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; 3. Patients with any uncontrolled active infection, including but not limited to patients with active tuberculosis (investigator 's judgment); 4. 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; 5. 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 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 or five half-lives before preconditioning 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. 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); 12. 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; 13. Patients with secondary plasma cell leukemia, Waldenström macroglobulinemia, POEMS syndrome, or primary light chain amyloidosis at screening; 14. Patients with any of the following cardiac conditions within 6 months prior to screening: 15. 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; 16. Patients with active autoimmune diseases, including but not limited to psoriasis, rheumatoid arthritis and other diseases requiring long-term immunosuppressive therapy; 17. Patients with second primary malignancies in addition to MM 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 18. Patients with symptomatic central nervous system (CNS) disease or suspected CNS metastases; 19. The patient is unable or unwilling to comply with protocol, or there are other reasons for being unsuitable to participate in this clinical study evaluated by investigators.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD and/or dose range | 12 months after CT0596 infusion | Evaluate Dose limited toxicity and recommended dosage range after CT0596 infusion |
| Adverse Events (AE) after CT0596 infusion | 12 months after CT0596 infusion | An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of very good partial response (VGPR) and above | 12 months after CT0596 infusion | 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 |
| Duration of response (DOR) | 12 months after CT0596 infusion | DOR is defined as the time from first achieving PR or better to confirmed disease progression or death from any cause |
| Minimal residual disease (MRD) negative rate | 12 months after CT0596 infusion | 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 |
| Time to response (TTR) | 12 months after CT0596 infusion | TTR defined as the time from the date of infusion to the date of initial assessment of PR or better according to IMWG2016 criteria |
| Progression-free survival (PFS) | 12 months after CT0596 infusion | PFS defined as the time from the date of infusion of the subject to the first assessment of confirmed disease progression or death from any cause according to IMWG2016 criteria, whichever occurs first. |
| Overall response rate (ORR) as assessed by the investigator | 12 months after CT0596 infusion | Overall response rate (ORR) defined as proportion of patients achieving partial response or better based on International Myeloma Working Group defined response criteria |
| Overall survival (OS) | 12 months after CT0596 infusion | OS defined as the time from the date of infusion of the subject to death from any cause |
| Cytokines in the peripheral blood after CT0596 infusion | 12 months after CT0596 infusion | Serum concentrations of interleukin (IL)-6 after CT0596 infusion |
| Area under the plasma concentration versus time curve (AUC) of CART cells | 12 months after CT0596 infusion | Area under the plasma concentration versus time curve (AUC) in plasma after infusion of CT0596 cells |
| In vivo persistence of CART cells | 12 months after CT0596 infusion] | CART cells duration in plasma after infusion of CT0596 cells |
| Peak value of CART cells | 12 months after CT0596 infusion | Time to peak expansion and peak expansion in plasma after infusion of CT0596 cells |
| Complete response/stringent complete response (CR/sCR) rate | 12 months after CT0596 infusion | Rate of complete response/stringent complete response (CR/sCR) defined as proportion of patients achieving CR or better based on IMWG defined response criteria. |
Countries
China
Outcome results
None listed