A Study of the Efficacy and Safety of Pomalidomide Capsules Combined With Low-Dose Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of permadomide capsules developed by Qilu Pharmaceutical Co., LTD.

Official Title
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A Multicenter, Open-Label, Single-Arm Clinical Study of the Efficacy and Safety of Pomalidomide Capsules Combined With Low-Dose Dexamethasone in Subjects With Relapsed and Refractory Multiple Myeloma

Conditions
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Multiple Myeloma, Recurrent or Refractory

Intervention / Treatment
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* Drug: Pomalidomide
* Drug: Dexamethasone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1.Subjects diagnosed with multiple myeloma according to the diagnostic criteria of Chinese Multiple Myeloma Diagnosis and Treatment Guidelines (Revised in 2020); 2.Must be ≥ 18 years of age,male or female, if the subject is of childbearing age and should use effective contraceptive methods, the subject must agree to comply with all contraceptive requirements: there are fertile women have to decide, at the same time take two reliable contraceptive methods (an effective contraceptive method is: tubal ligation, intrauterine contraceptive device, hormone (birth control pills, needles, patch, vaginal ring or implants) or partner vasectomy, another effective birth control method is: male or synthetic rubber condom, diaphragm or cervical cap). Unless hysterectomy is performed, effective contraception is required even if there is a history of infertility. Fertile men must use rubber or synthetic condoms at all times during the use of this product and during sexual contact with fertile women within 28 days of discontinuation of this product, even if participants have successfully had a vasectomy. 3. Received at least two previous treatments (in different treatment regimens or the same regimen, including at least 2 cycles of lenalidomide and 2 cycles of proteasome inhibitors [such as bortezomib or ixazomib]) Relapse of multiple myeloma or ineffective to the last treatment (definition of last treatment ineffective: disease progression during the use of the treatment plan or disease progression within 60 days after the completion of the treatment plan), the last treatment plan is not limited; 4. Multiple myeloma subjects with measurable M protein, i.e., at least one of the following 3 assays: Serum M protein≥0.5g/dL (5g/L); Urine M protein≥200mg/24h; Determination of serum free light chain: in the case of abnormal serum free light chain ratio, the level of involved free light chain is ≥10 mg/dL (100 mg/L); 5. Hematology meets the following conditions: 1) ANC≥1.0 x10^9/L (including ANC≥1.0x10^9/L supported by G-CSF); 2) PLT≥50 x10^9/L； 3) When plasma cells in bone marrow ≥50%, no specific requirements for neutrophil count, platelet ≥30 x10^9/L can be selected; 6. Liver and kidney function tests meet the following conditions: TBIL ≤ 2.0mg/dL； ALT、AST ≤ 3.0 x ULN； 3) Serum creatinine ≤ 3.0 mg/dL or creatinine clearance rate ≥ 30 mL/min; 7. Those who can accept and can use antithrombotic drugs, such as low molecular weight heparin sodium or aspirin; 8. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2, expected survival ≥ 3 months; 9. There must be a washout period of ≥ 2 weeks (14 days) from the last treatment (excluding dexamethasone treatment); 10. Subjects voluntarily joined the study and signed a written informed consent. Exclusion Criteria: Subjects who cannot tolerate thalidomide, lenalidomide, pomalidomide and other types of drug treatment according to the judgment of the investigator. Subjects who have had allergic reactions to immunomodulators similar to pomalidomide, dexamethasone or components contained in the drug; Diagnosis of non-secretory MM (non-secretory subjects or subjects with a small amount of free light chain but less than 100mg/L) in multiple myeloma; Subjects with active new thrombosis or unwilling to undergo antithrombotic therapy; The subjects are suffering from other tumors at the same time or have a past history of tumors, or have undergone anti-tumor treatment (including major surgery) within the last 4 weeks, except for the following tumor diseases or those who have lived without tumors for ≥ 3 years so far: skin base Cell carcinoma, squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, incidental histologic findings of prostate cancer (TNM clinical stage T1a or T1b), or treated prostate cancer; Subjects suffering from central nervous system diseases and requiring treatment; Subjects with peripheral neuropathy ≥ grade 3; Subjects who need to use immunosuppressive or steroid drugs for a long time; Known subjects with hepatitis B virus (HBV-DNA ≥ 1×10^3 copies/mL or HBV-DNA > 200 IU/mL) or hepatitis C virus (HCV) activity, or human immunodeficiency virus (HIV) ) serologically positive; Subject has any of the following: 1) According to the NYHA classification standard, cardiac insufficiency grade 2 or above; 2) Myocardial infarction occurred within one year; 3) poorly controlled angina pectoris, including variant angina pectoris; 11. Subjects have serious infectious diseases at the same time; 12. Subjects planning to become pregnant or unable to take reliable contraceptive measures; 13. Women who are pregnant or breastfeeding; 14. Subjects who have received allogeneic hematopoietic stem cell transplantation within 12 months, or who have active graft-versus-host disease (GVHD) or who require immunosuppressive therapy after 12 months of allogeneic hematopoietic stem cell transplantation； 15. Those who participated in other clinical trials and received experimental drugs within one month before the first drug use.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Permadomide + Low-Dose Dexamethasone<br>Participants received 4 mg pomalidomide administered by mouth on Days 1 to 21 of each 28-day treatment cycle and 40 mg dexamethasone administered by mouth once per day on Days 1, 8, 15, and 22 of each 28-day cycle until disease progression. | Drug: Pomalidomide<br>* 4 mg pomalidomide capsules administered orally<br>Drug: Dexamethasone<br>* 40 mg dexamethasone tablets administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Response Rate(ORR) | Statistical analysis of ORR of primary efficacy will be based on IRC remission assessment results, as well as the investigator's remission assessment.Strict Complete Response (sCR) + Complete Response (CR) + Partial Response (PR) + Very Good PR (VGPR). | From randomization through the study follow-up phase; up to the data cut-off of 1 December 2023; Maximum time on follow-up was 104 weeks. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of remission(DoR) | The time from the first observation of at least partial remission (PR) to disease progression (PD) or death from any cause is whichever comes first. | The time from the first observation of at least partial remission (PR) to disease progression (PD) or death from any cause is whichever comes first, assessed up to 104 weeks. | 
| Progression-free survival(PFS) | The time between the first dose of this trial and the onset of progression (evaluated according to IMWG efficacy criteria listed in the China Guidelines for the Diagnosis and Treatment of Multiple Myeloma 2020 (see attachment)) or death. | up to 104 weeks | 
| Overall survival(OS) | The time between enrollment for the first dose of the study and the death of the patient from any cause (the last follow-up date for the lost subjects and the end date for the patients who were still alive at the end of the study). | up to 104 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Permadomide capsules