IMM01+Azacitidine VS Placebo +Azacitidine in Patients With Newly Diagnosed Chronic Myelomonocytic Leukemia (CMML1-2)
- Conditions
- Chronic Myelomonocytic Leukemia
- Interventions
- Registration Number
- NCT06647862
- Lead Sponsor
- ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
- Brief Summary
This study is a randomized, controlled, double-blind, multicenter, phase Ⅲ clinical study to evaluate the efficacy of IMM01(timdarpacept) in combination with azacitidine versus placebo in combination with azacitidine in patients with newly diagnosed chronic leukemia monocytic (CMML1-2).Primary endpoint are Complete remission rate and Overall survival.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 170
- Age ≥ 18 years old, regardless of gender;
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
- Life expectancy ≥ 12 weeks;
- Patients with CMML diagnosed according to WHO 2016 criteria, including CMML-1 and CMML-2;
- White blood cell count ≤ 13×10⁹/L before the first treatment with the study drug (hydroxyurea and leukapheresis are allowed, but not within 3 days prior to the first treatment with the study drug).
- Patients must be treatment-naïve to any hypomethylating agents (e.g., azacitidine, decitabine), chemotherapy or allogeneic stem cell transplant for CMML. Immunomodulators ( lenalidomide), immunosuppressants (antithymocyte globulin, cyclosporine), targeted agents (ruxolitinib), etc. are also excluded, as these agents are considered disease-modifying therapies. Note: During screening and study participation, subjects may continue oral corticosteroids for diseases other than CMML (e.g. asthma) at a stable daily dose equivalent to ≤ 10 mg prednisone. In addition, supportive care in the form of blood transfusions or growth factors is not considered prior therapy in this case and is permitted prior to and as needed during the study.
- Previous treatment with anti-CD47 monoclonal antibody/SIRPα fusion protein;
- History of allogeneic stem cell transplant and other organ transplants; Patients who have undergone autologous haematopoietic stem cell transplant;
- Prior diagnosis of: therapy-related myelodysplastic syndrome(t-MDS); MDS evolved from a pre-existing myeloproliferative neoplasm (MPN) ;MDS/MPN including atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN. Patients positive for BCR-ABL fusion genes, PDGFRA, PDGFRB, and FGFR1 rearrangements need to be excluded;
- Current or history of central nervous system (CNS) leukemia, extramedullary leukemia, or myeloid sarcoma;
- Diagnosis of other malignant neoplasms within 3 years prior to the first dose. Exceptions: a. Radically treated cervical carcinoma in situ or non-melanoma skin cancer; b. a second primary cancer that has been curatively treated and has no recurrence within three years;
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description IMM01 in combination with azacitidine Azacitidine One treatment cycle consists of 4 weeks (28 days). IMM01(timdarpacept) will be administered once weekly, and azacitidine will be administered from Day 1 to Day 7 of each cycle. placebo in combination with azacitidine Azacitidine One treatment cycle consists of 4 weeks (28 days). Placebo will be administered once weekly, and azacitidine will be administered on days 1-7 of each cycle. placebo in combination with azacitidine Placebo One treatment cycle consists of 4 weeks (28 days). Placebo will be administered once weekly, and azacitidine will be administered on days 1-7 of each cycle. IMM01 in combination with azacitidine IMM01 One treatment cycle consists of 4 weeks (28 days). IMM01(timdarpacept) will be administered once weekly, and azacitidine will be administered from Day 1 to Day 7 of each cycle.
- Primary Outcome Measures
Name Time Method Complete remission( CR) rate approximately 24 months CR rate: CR rate determined by Independent Review Committee (IRC) based on IWG2006 MDS efficacy evaluation criteria;
Overall survival (OS) approximately 24 months Overall survival (OS): Time from randomization to death from any cause;
- Secondary Outcome Measures
Name Time Method Event-free survival(EFS) approximately 24 months Time from randomization to transformation to AML or death from any cause, whichever occurs first
Progression-free survival(PFS) approximately 24 months Time from randomization to transformation to AML or death from any cause, whichever occurs first
Time to response (TTR) approximately 24 months time from first dose to first occurrence of CR, partial remission (PR), marrow complete remission (mCR) ± hematologic improvement (HI), HI, assessed by IRC and investigators, respectively
overall response rate(ORR) approximately 24 months is defined as the proportion of the analysis population achieving CR, PR, mCR±HI, or HI
Duration of response(DOR) approximately 24 months is defined as the time from the first occurrence of CR, PR, mCR±HI, or HI to disease progression or death from any cause, whichever occurs first
Red blood cell transfusion independence (RTI) approximately 24 months the proportion of patients who did not receive red blood cell (or whole blood) transfusion for 8 consecutive weeks during the study treatment period among patients who required transfusion at baseline.
Complete remission(CR) rate approximately 24 months CR rate determined by IRC based on IWG2006 MDS efficacy evaluation criteria assessed by the investigator;
Time to transformation to acute myeloid leukemia approximately 24 months Time from initiation of study treatment to transformation to AML; defined as ≥ 20% blasts in the bone marrow or peripheral blood by manual differential count, according to the 2016 WHO classification criteria.
Trial Locations
- Locations (43)
Anhui Provincial Hospital
🇨🇳Hefei, Anhui, China
China-Japan Friendship Hospita
🇨🇳Beijing, Beijing, China
The First Affiliated Hospital of Chongqing Medical University
🇨🇳Chongqing, Chongqing, China
First Hospital of Lanzhou University
🇨🇳Lanzhou, Gansu, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Gaungxi, China
Nanfang Hospital, Southern Medical University
🇨🇳Guangzhou, Guangdong, China
Shenzhen Second People's Hospital
🇨🇳Shenzhen, Guangdong, China
Affiliated Hospital of Guizhou Medical University
🇨🇳Guiyang, Guizhou, China
Affiliated Hospital of Hebei University
🇨🇳Shijiazhuang, Hebei, China
Xiangyang Central Hospital
🇨🇳Xiangyang, Hubei, China
Xiangya Hospital Central South University
🇨🇳Changsha, Hunan, China
Changzhou First People's Hospital
🇨🇳Changzhou, Jiangsu, China
Jiangsu Province Hospital
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Affiliated Hospital of Xuzhou Medical University
🇨🇳Xuzhou, Jiangsu, China
Jiangsu Subei People's Hospital
🇨🇳Yangzhou, Jiangsu, China
Qilu Hospital of Shandong University
🇨🇳Jinan, Shandong, China
Shaanxi Provincial People's Hospital
🇨🇳Xi'an, Shanxi, China
Sichuan Provincial People's Hospital
🇨🇳Chengdu, Sichuan, China
Yibin Second People's Hospital
🇨🇳Yibin, Sichuan, China
The First Affiliated Hospital of Xinjiang Medical University
🇨🇳Ürümqi, Xinjiang, China
Ningbo First Hospital
🇨🇳Ningbo, Zhejiang, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Zhujiang Hospital of Southern Medical University
🇨🇳Zhujiang, Guangdong, China
Guangdong Provincial People's Hospital
🇨🇳Guangzhou, Guangzhou, China
The Second Hospital of Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
Harbin First Hospital
🇨🇳Harbin, Heilongjiang, China
First Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou, Henan, China
Henan Cancer Hospital
🇨🇳Zhengzhou, Henan, China
Henan Provincial People's Hospital
🇨🇳Zhengzhou, Henan, China
The First Affiliated Hospital of Henan University of Science and Technology
🇨🇳Zhengzhou, Henan, China
Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
🇨🇳Wuhan, Hubei, China
Zhongnan Hospital Affiliated to Wuhan University
🇨🇳Wuhan, Hubei, China
Zhongda Hospital affiliated to Southeast University
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Nanchang University
🇨🇳Nanchang, Jiangxi, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
The First Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College;
🇨🇳Tianjin, Tianjin, China
The Second Affiliated Hospital of Kunming Medical University
🇨🇳Kunming, Yunnan, China
The First Affiliated Hospital, Zhejiang University School of Medicine
🇨🇳Hangzhou, Zhejiang, China
Peking University People's Hospital
🇨🇳Beijing, China
Tianjin People's Hospital
🇨🇳Tianjin, China