Clinical trial NCT06647862: IMM01+Azacitidine VS Placebo +Azacitidine in Patients With Newly Diagnosed Chronic Myelomonocytic Leukemia (CMML1-2)
Official title: A Randomized, Controlled, Double-Blind, Multicenter, Phase Ⅲ Study to Evaluate the Efficacy and Safety of IMM01 (Timdarpacept) in Combination With Azacitidine in Patients With Newly Diagnosed Chronic Myelomonocytic Leukemia (CMML1-2)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Chronic Myelomonocytic Leukemia
Lead sponsor: ImmuneOnco Biopharmaceuticals (Shanghai) Inc.
Sponsor class: OTHER
First posted: 2024-10-18
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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;

Primary outcomes:
measure: Complete remission( CR) rate
timeFrame: approximately 24 months
measure: Overall survival (OS)
timeFrame: approximately 24 months
Secondary outcomes:
measure: Event-free survival(EFS)
timeFrame: approximately 24 months
measure: Progression-free survival(PFS)
timeFrame: approximately 24 months
measure: Time to response (TTR)
timeFrame: approximately 24 months
measure: overall response rate(ORR)
timeFrame: approximately 24 months
measure: Duration of response(DOR)
timeFrame: approximately 24 months
measure: Red blood cell transfusion independence (RTI)
timeFrame: approximately 24 months
measure: Complete remission(CR) rate
timeFrame: approximately 24 months
measure: Time to transformation to acute myeloid leukemia
timeFrame: approximately 24 months
Other outcomes:
Locations:
city: Hefei
country: China
facility: Anhui Provincial Hospital
state: Anhui
city: Beijing
country: China
facility: China-Japan Friendship Hospita
state: Beijing
city: Chongqing
country: China
facility: The First Affiliated Hospital of Chongqing Medical University
state: Chongqing
city: Lanzhou
country: China
facility: First Hospital of Lanzhou University
state: Gansu
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Gaungxi
city: Guangzhou
country: China
facility: Nanfang Hospital, Southern Medical University
state: Guangdong
city: Shenzhen
country: China
facility: Shenzhen Second People's Hospital
state: Guangdong
city: Zhujiang
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangzhou
city: Guiyang
country: China
facility: Affiliated Hospital of Guizhou Medical University
state: Guizhou
city: Shijiazhuang
country: China
facility: Affiliated Hospital of Hebei University
state: Hebei
city: Shijiazhuang
country: China
facility: The Second Hospital of Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: Harbin First Hospital
state: Heilongjiang
city: Zhengzhou
country: China
facility: First Affiliated Hospital of Zhengzhou University
state: Henan
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Henan University of Science and Technology
state: Henan
city: Wuhan
country: China
facility: Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital Affiliated to Wuhan University
state: Hubei
city: Xiangyang
country: China
facility: Xiangyang Central Hospital
state: Hubei
city: Changsha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: Changzhou
country: China
facility: Changzhou First People's Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: Zhongda Hospital affiliated to Southeast University
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Xuzhou
country: China
facility: Affiliated Hospital of Xuzhou Medical University
state: Jiangsu
city: Yangzhou
country: China
facility: Jiangsu Subei People's Hospital
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shenyang
country: China
facility: The First Hospital of China Medical University
state: Liaoning
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Xi'an
country: China
facility: Shaanxi Provincial People's Hospital
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Yibin
country: China
facility: Yibin Second People's Hospital
state: Sichuan
city: Tianjin
country: China
facility: Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College;
state: Tianjin
city: Ürümqi
country: China
facility: The First Affiliated Hospital of Xinjiang Medical University
state: Xinjiang
city: Kunming
country: China
facility: The Second Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
city: Ningbo
country: China
facility: Ningbo First Hospital
state: Zhejiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: Peking University People's Hospital
city: Tianjin
country: China
facility: Tianjin People's Hospital
Study officials:
affiliation: Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
name: zhijian xiao, PHD
role: PRINCIPAL_INVESTIGATOR
affiliation: Zhejiang University
name: Hongyan Tong, PHD
role: PRINCIPAL_INVESTIGATOR
References: