A Study to Evaluate the Safety and Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of TJ011133 as Monotherapy and in Combination With Azacitidine (AZA) in Patients With Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS)

NCT04202003 | Completed Phase 1

• 1 other identifier: TJ011133AML102
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 26

Brief Summary

This study is a phase I/II study of TJ011133 as Monotherapy and in Combination with Azacitidine (AZA) in Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndrome (MDS). This study include Phase I and Phase IIa study. Phase I study ClinicalTrials.gov ID is NCT04202003 and this is for phase IIa study. Phase IIa study is designed to preliminarily assess the efficacy and safety of TJ011133 in combination with AZA as first-line treatment in patients with newly diagnosed AML who are intolerant to standard induction chemotherapy or patients with treatment naive, intermediate and high-risk MDS.

Conditions

Acute Myeloid Leukemia (AML); Myelodysplastic Syndromes(MDS)

Outcome Measures

Primary Outcomes (4)

• Dose Limiting Toxicities(DLT)

  To evaluate the safety and tolerance of TJ011133 monotherapy in patients with r/r AML or MDS

  28days after first dose

• Maximum tolerable dose(MTD)

  To explore the maximum tolerable dose (MTD) of TJ011133 monotherapy for patients with r/r AML or MDS, the recommended phase II dose (RP2D) and the optimal dosage regimen.

  Through study completion, an average of 1 year

• Recommended phase II dose

  Recommended phase II dose (RP2D)

  Through study completion, an average of 1 year

• Complete response rate (CR rate) only for phase 2a

  Preliminary efficacy endpoints (only for Phase 2a): for response assessment in AML/MDS patients, the complete response rate (CR rate) will be evaluated according to the ELN2017/IWG 2006 criteria

  Through study completion，an average of 1 year

Study Arms (1)

TJ011133

EXPERIMENTAL

This is an open-label Phase 1/2a clinical study. The study will be conducted in two parts: Part I: Phase 1 dose escalation, TJ011133 is tentatively scheduled to be administered once weekly in 28-day treatment cycles;Part II: Phase 2a study TJ011133 will be administered at a dose of 30 mg/kg once weekly, and AZA will be administered at a dose of 75 mg/m2 by subcutaneous injection for 7 consecutive days from D1 to D7 in 28-day treatment cycles.

Drug: TJ011133

Interventions

TJ011133 DRUG

This is an open-label Phase 1/2a clinical study. The study will be conducted in two parts: Part I: Phase 1 dose escalation, TJ011133 is tentatively scheduled to be administered once weekly in 28-day treatment cycles;Part II: Phase 2a study TJ011133 will be administered at a dose of 30 mg/kg once weekly, and AZA will be administered at a dose of 75 mg/m2 by subcutaneous injection for 7 consecutive days from D1 to D7 in 28-day treatment cycles.

TJ011133

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Phase 1 single dose escalation:
• Male or female, aged ≥ 18 and ≤ 70 years at the time of signing informed consent form;
• For the disease under study, enrollment may be considered if one of the following is satisfied:
• Subjects must be with pathologically diagnosed as acute myeloid leukemia (AML) according World Health Organization (WHO) 2016 classification criteria, with the exception of acute promyelocytic leukemia; it is a recurrent or refractory disease without other available appropriate conventional treatments;
• Subjects with intermediate- and high-risk relapsed/refractory MDS (IPSS-R score \>3.5) who are pathologically confirmed and meeting the diagnostic criteria of World Health Organization (WHO) 2016 or who are unable to tolerate the treatment of demethylation drugs or other drugs (e.g., treatment-emergent Grade 3 or higher drug-related hepatic and/or renal toxicities leading to permanent withdrawal during treatment), and the investigator judges that there is no other appropriate treatment;
• For patients with MDS, a blast percentage of \< 20% is required in bone marrow aspiration smear or bone marrow biopsy pathology at screening;
• ECOG score 0-2;
• Subjects have been recovered from the toxicity of previous anti-AML/MDS treatments (according to NCI CTC AE 5.0 ≤ Grade 1, except alopecia) ;
• Subjects must have adequate liver function, renal function and coagulation function. The laboratory tests within 7 days before the first dose should meet the following requirements:
• Liver function:
• Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN);
• AST and ALT ≤ 2.5 × ULN.
• Renal function:
• Serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 50 mL/min according to the Cockcroft-Gault equation (Appendix 5).
• Coagulation function:

You may not qualify if:

• Phase 1 single dose escalation:
• Previously received treatment with other drug therapies targeting CD47;
• Previously received CAR-T cell therapy;
• Previously received treatment with PD1 or PDL1 antibody;
• Previously received or planned to receive allogeneic stem cell transplantation during the study, or autologous stem cell transplantation within 3 months prior to the first dose of study drug;
• Subjects have received chemotherapy, immunotherapy, radiotherapy, major surgery within 4 weeks prior to the first dose;
• Subjects' cardiac function meet any of the following criteria:
• Subjects have any kind of clinically significant rhythm abnormalities or conduction abnormalities that require clinical intervention;
• Subjects have congenital QT prolongation syndrome or QTc \> 450 msec in men, QTc \> 470 msec in women (QTc calculated using Fridericia's correction formula \[Appendix 6\]), or on medications that may cause QT prolongation or torsades de pointes;
• Subjects have any kind of clinically significant cardiovascular diseases, including acute myocardial infarction, unstable angina, coronary artery bypass surgery or peripheral artery bypass surgery, cerebrovascular events (thromboembolic or hemorrhagic cerebrovascular events, excluding transient ischemic attack), New York Heart Association (NYHA) (Appendix 7) ≥ Grade 3 congestive cardiac failure, or left ventricular ejection fraction (LVEF) \< 40% within 3 months prior to enrollment; Phase 2a combination therapy
• Previously received treatment with demethylated drugs or cytotoxic drugs in patients with MDS;
• Previously received any anti-tumor therapy for AML;
• AML with a good prognosis, including cytogenetic alterations, such as t (8;21), inv (16) or t (16;16) or t (15;17);
• Subjects are known to have allergy to AZA or mannitol;
• Subjects' cardiac function meet any of the following criteria:

Sponsors & Collaborators

• TJ Biopharma Co., Ltd.: lead

Study Sites (26)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100032, China

Location

Peking University International Hospital

Beijing, Beijing Municipality, 102206, China

Location

Beijing Boren Hospital

Beijing, Beijing Municipality, China

Location

The First Affiliated Hospital of Chongqing Medical University

Chongqing, Chongqing Municipality, 400016, China

Location

The First Affiliated Hospital of Xiamen University

Xiamen, Fujian, 361003, China

Location

Guangdong Provincial People's Hospital

Guangzhou, Guangdong, 510000, China

Location

Zhujiang Hospital Of Southern Medical University

Guangzhou, Guangdong, 510280, China

Location

Nanfang Hospital

Guangzhou, Guangdong, 510515, China

Location

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, China

Location

Shenzhen Second People's Hospital

Shenzhen, Guangdong, 518020, China

Location

The Affiliated Hospital of Guizhou Medical University

Guiyang, Guizhou, 550004, China

Location

The Second Hospital of HeBei Medical University

Shijiazhuang, Hebei, 050000, China

Location

Henan Cancer Hospital

Zhengzhou, Henan, 450008, China

Location

Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

Jiangsu Province Hospital

Suzhou, Jiangsu, 221006, China

Location

The First Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

The First Hospital of China Medical University

Shenyang, Liaoning, 110001, China

Location

Qilu Hospital of Shandong University

Jinan, Shandong, 266000, China

Location

Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 200000, China

Location

Shanghai Sixth People's Hospital

Shanghai, Shanghai Municipality, 200233, China

Location

The Second Affiliated Hospital of Xi'an Jiaotong University（Xibei Hospital）

Xi’an, Shanxi, 710004, China

Location

Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical

Tianjin, Tianjin Municipality, 300020, China

Location

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

Location

The second Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650101, China

Location

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310003, China

Location

The Second Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310009, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 13, 2019
• First Posted: December 17, 2019
• Study Start: March 25, 2020
• Primary Completion: December 15, 2023
• Study Completion: December 15, 2023
• Last Updated: April 15, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (26)