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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Myeloma; Recurrent or Refractory
• Intervention / Treatment: Drug: Pomalidomide; Drug: Dexamethasone

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100000
      • Beijing Chaoyang Hospital, Capital Medical University
    • Beijing, Beijing, China, 100000
      • Shengjing Hospital Affiliated to China Medical University
  • Guangdong
    • Foshan, Guangdong, China, 528000
      • Foshan First People's Hospital
    • Guangzhou, Guangdong, China, 510080
      • The First Affiliated Hospital of Sun Yat-sen University
    • Guangzhou, Guangdong, China, 510000
      • Guangzhou First People's Hospital
    • Guangzhou, Guangdong, China, 510000
      • The First Affiliated Hospital of Guangzhou Medical University
  • Guizhou
    • Guiyang, Guizhou, China, 550000
      • Guizhou Provincial People's Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 050000
      • The Third Hospital of Hebei Medical University
    • Shijiazhuang, Hebei, China, 050000
      • The Fourth Hospital of Hebei Medical University
  • Henan
    • Zhengzhou, Henan, China, 450000
      • Henan Tumor Hospital
  • Hunan
    • Hengyang, Hunan, China, 421200
      • The First Affiliated Hospital of Nanhua University
  • Shandong
    • Jinan, Shandong, China, 250000
      • Shandong University Qilu Hospital
    • Qingdao, Shandong, China, 266000
      • Affiliated Hospital of Qingdao University
    • Weifang, Shandong, China, 261000
      • Weifang People's Hospital
    • Weihai, Shandong, China, 264200
      • Weihai Central Hospital
  • Shanxi
    • Taiyuan, Shanxi, China
      • The Second Hospital of Shanxi Medical University
    • Taiyuan, Shanxi, China, 030000
      • Shanxi Cancer Hospital
    • Xi'an, Shanxi, China, 710000
      • Second Affiliated Hospital of Xi 'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610000
      • Sichuan Provincial People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300000
      • Tianjin Cancer Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650000
      • Yunnan Cancer Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310000
      • The First Affiliated Hospital of Zhejiang University Medical College (Hematology)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. 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.
2. 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:

1. Serum M protein≥0.5g/dL (5g/L);
2. Urine M protein≥200mg/24h;
3. 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:

1. TBIL ≤ 2.0mg/dL；
2. 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:

1. Subjects who cannot tolerate thalidomide, lenalidomide, pomalidomide and other types of drug treatment according to the judgment of the investigator.
2. Subjects who have had allergic reactions to immunomodulators similar to pomalidomide, dexamethasone or components contained in the drug;
3. 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;
4. Subjects with active new thrombosis or unwilling to undergo antithrombotic therapy;
5. 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;
6. Subjects suffering from central nervous system diseases and requiring treatment;
7. Subjects with peripheral neuropathy ≥ grade 3;
8. Subjects who need to use immunosuppressive or steroid drugs for a long time;
9. 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;
10. 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.

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: Permadomide + Low-Dose Dexamethasone; 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; 4 mg pomalidomide capsules administered orally; Drug: Dexamethasone; 40 mg dexamethasone tablets administered orally

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Wenming Chen, MD, PhD, Beijing Chao Yang Hospital; Principal Investigator: Juan Li, MD, PhD, First Affiliated Hospital, Sun Yat-Sen University; Principal Investigator: Hongmei Jing, MD, PhD, Peking University Third Hospital; Principal Investigator: Huo Tan, MD, PhD, The First Affiliated Hospital of Guangzhou Medical University; Principal Investigator: Shunqing Wang, MD, PhD, Guangzhou First People's Hospital; Principal Investigator: Ying Zhao, MD, PhD, Foshan First People's Hospital; Principal Investigator: Xun Lai, MD, PhD, Yunnan Cancer Hospital; Principal Investigator: Qing Wang, MD, PhD, Guizhou Provincial People's Hospital; Principal Investigator: Jinqiao Zhang, MD, PhD, Hebei Medical University Third Hospital; Principal Investigator: Lihong Liu, MD, PhD, The Fourth Hospital of Hebei Medical University; Principal Investigator: Baijun Fang, MD, PhD, Henan Tumor Hospital; Principal Investigator: Junjun Li, MD, PhD, The First Affiliated Hospital of Nanhua University; Principal Investigator: Binghua Wang, MD, PhD, Weihai Central Hospital; Principal Investigator: Wei Yang, MD, PhD, Shengjing Hospital Affiliated to China Medical University; Principal Investigator: Wei Wang, MD, PhD, The Affiliated Hospital of Qingdao University; Principal Investigator: Aili He, MD, PhD, Second Affiliated Hospital of Xi 'an Jiaotong University; Principal Investigator: Yafei Wang, MD, PhD, Tianjin Cancer Hospital; Principal Investigator: Jie Jin, MD, PhD, The First Affiliated Hospital of Zhejiang University Medical College (Hematology); Principal Investigator: Xuehong Ran, MD, PhD, Weifang People's Hospital; Principal Investigator: Jiao Chen, MD, PhD, Sichuan Provincial People's Hospital; Principal Investigator: Liping Su, MD, PhD, Shanxi Province Cancer Hospital; Principal Investigator: Yanping Ma, MD, PhD, Second Hospital of Shanxi Medical University; Principal Investigator: Yanping Song, MD, PhD, Xi 'an Central Hospital; Principal Investigator: Congmeng Lin, MD, PhD, Zhangzhou Hospital, Fujian Province; Principal Investigator: Quanyi Lu, MD, PhD, Zhongshan Hospital Xiamen University; Principal Investigator: Da Gao, MD, PhD, Affiliated Hospital of Inner Mongolia Medical University; Principal Investigator: Wenhong Lai, MD, PhD, The First Affiliated Hospital of Gannan Medical College; Principal Investigator: Jianping Hao, MD, PhD, First Affiliated Hospital of Xinjiang Medical University; Principal Investigator: Taiwu Xiao, MD, PhD, Liaocheng People's Hospital; Principal Investigator: Zhen Cai, MD, PhD, The First Affiliated Hospital of Zhejiang University Medical College (Transplant Center); Principal Investigator: Xin Zhou, MD, PhD, Wuxi People's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 4, 2021
• Primary Completion (Anticipated): June 1, 2022
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: January 24, 2022
• First Submitted That Met QC Criteria: February 9, 2022
• First Posted (Actual): February 11, 2022

Study Record Updates

• Last Update Posted (Actual): February 11, 2022
• Last Update Submitted That Met QC Criteria: February 9, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Permadomide capsules
• 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; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Pomalidomide
• Other Study ID Numbers: QL-YK4-056-003

Drug and device information, study documents

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