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Acute Myeloid Leukemia (AML)Phase 1/2NCT04202003

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)

A Phase 1/2 study testing TJ011133 in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes(MDS), run by TJ Biopharma Co., Ltd. at 26 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
TJ011133
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
105 participants
Where
26 sitesChina
Study dates
25 Mar 2020to 15 Dec 2023
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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;
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  • 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:
  • International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN;
  • Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
  • Subjects for Phase 2a combination therapy:
  • Male or female, aged ≥ 18 years at the time of signing informed consent form;
  • For the disease under study, enrollment may be considered only if the following conditions are met:
  • Newly diagnosed AML with intolerance to standard induction chemotherapy/intermediate- and high-risk (International Prognostic Scoring System IPSS-R) MDS (only applicable for Phase 2a study); symptomatic treatment such as hydroxycarbamide, erythropoietin, and/or hematopoietic growth factors are allowed within 7 days of the first dose;
  • The subject's ECOG score has to meet the following criteria:
  • Newly diagnosed AML with intolerance to standard induction
  • Newly diagnosed intermediate- and high-risk MDS: ECOG score 0 - 2
  • 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); total bilirubin ≤ 3 × ULN is allowed for subjects aged 18 - 74 years (only for newly diagnosed AML subjects who are intolerant to standard induction chemotherapy)
  • AST and ALT ≤ 3 × ULN.
  • Renal function:
  • -Estimated creatinine clearance ≥ 50 mL/min according to the Cockcroft-Gault equation (Appendix 5); creatinine clearance ≥ 30 mL/min is allowed for subjects aged 18 - 74 years (only for newly diagnosed AML subjects who are intolerant to standard induction chemotherapy)
  • Coagulation function:
  • International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN;
  • Activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN.
  • All subjects:
  • Expected survival ≥ 12 weeks;
  • White blood cell count (WBC) ≤ 25 × 103/μL within 7 days prior to the first dose (hydroxycarbamide or leukapheresis is allowed to meet this criterion);
  • Subjects must be willing to provide available diagnostic evidence or undergo bone marrow aspiration and biopsy before study treatment, and must be willing to undergo bone marrow aspiration and biopsy after receiving study treatment;
  • Subjects must give informed consent before starting the study and sign written consent voluntarily by themselves (or their legal representatives). Subjects or their legal representatives should be able to communicate well with investigators and agree to adhere with the study protocol and complete the study.

Who cannot join

  • 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;
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  • 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:
  • Subjects have any kind of clinically significant rhythm abnormalities or conduction abnormalities that require clinical intervention;
  • Subjects have congenital QT prolongation syndrome or taking drugs 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 within 3 months prior to enrollment;
  • Subjects have undergone major surgery within 4 weeks prior to the first dose;
  • All subjects:
  • Subjects have received vaccination within 4 weeks prior to the first dose and/or planned vaccination after participating in the study;
  • Subjects have received clinical trial drug treatment within 4 weeks prior to the first dose or currently participating in other interventional clinical trials;
  • Subjects are known to have hereditary or acquired hemorrhagic disorders;
  • Subjects have hypertension uncontrollable with drug therapy (systolic blood pressure ≥ 140 mmHg, or diastolic blood pressure ≥ 90 mmHg at rest);
  • Subjects suffer from disease that requires long-term use of systemic steroid therapy or other immunosuppressive therapy. However, subjects who use physiologic replacement doses of hydrocortisone or drugs of equivalent doses (Appendix 8), i.e., up to 20 mg of hydrocortisone (or 5 mg of prednisone) in the morning and up to 10 mg of hydrocortisone (or 2.5 mg of prednisone) at night, may be considered for enrollment;
  • Subjects are known to have central nervous system (CNS) involvement;
  • Subjects are known to have HIV infection (anti-HIV positive), active hepatitis B (HBsAg positive, or HBcAb positive and HBV-DNA PCR positive), or active hepatitis C (anti-HCV antibody positive and HCV-RNA PCR positive), or syphilis infection (anti-TP test positive);
  • Subjects have a history of solid organ transplantation;
  • Subjects plan to receive other anti-tumor therapies, including but not limited to chemotherapy, biotherapy, immunotherapy, hormone therapy and traditional Chinese medicine, while participating in the study;
  • Subjects have a history of autoimmune disease or active autoimmune disease;
  • Subjects have uncontrolled active infection;
  • Subjects have severe electrolyte disturbances that cannot be corrected;
  • Subjects have a history of other malignancies, except for clinically cured malignancies (no relapse for at least 5 years), cured carcinoma in situ, and skin cancer other than malignant melanoma;
  • Subjects have a history of psychotropic drug abuse and are unable to quit or have mental disorders, or have concomitant diseases that seriously endanger patients' safety or hinder the study completion at the discretion of investigators;
  • Subjects are women during pregnancy or lactation, or women and men with fertility planning;
  • The investigators consider that patients have other factors that may affect the results of the study and interfere with their full participation in the study, including previous or existing health conditions or medical or laboratory abnormalities, or put them at high risk.
  • Subjects with MDS who meet any of the following must also be excluded:
  • Subjects have uncorrected serum folic acid deficiency or vitamin B12 deficiency;
  • MDS transformed from previously existing myeloproliferative tumors (MPN) or MDS/MPN types conforming to WHO 2016 classification standard include chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML), etc..

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

China26 sites

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100032

  • Peking University International Hospital

    Beijing, Beijing Municipality, 102206

  • Beijing Boren Hospital

    Beijing, Beijing Municipality

  • The First Hospital of Jilin University

    Changchun, Jilin, 130021

  • The First Affiliated Hospital of Chongqing Medical University

    Chongqing, Chongqing Municipality, 400016

  • Guangdong Provincial People's Hospital

    Guangzhou, Guangdong, 510000

  • Zhujiang Hospital Of Southern Medical University

    Guangzhou, Guangdong, 510280

  • Nanfang Hospital

    Guangzhou, Guangdong, 510515

  • Sun Yat-sen University Cancer Center

    Guangzhou, Guangdong

  • The Affiliated Hospital of Guizhou Medical University

    Guiyang, Guizhou, 550004

  • The First Affiliated Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310003

  • The Second Affiliated Hospital, Zhejiang University School of Medicine

    Hangzhou, Zhejiang, 310009

  • Qilu Hospital of Shandong University

    Jinan, Shandong, 266000

  • The second Affiliated Hospital of Kunming Medical University

    Kunming, Yunnan, 650101

  • Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

    Shanghai, Shanghai Municipality, 200000

  • Shanghai Sixth People's Hospital

    Shanghai, Shanghai Municipality, 200233

  • The First Hospital of China Medical University

    Shenyang, Liaoning, 110001

  • Shenzhen Second People's Hospital

    Shenzhen, Guangdong, 518020

  • The Second Hospital of HeBei Medical University

    Shijiazhuang, Hebei, 050000

  • Jiangsu Province Hospital

    Suzhou, Jiangsu, 221006

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

    Tianjin, Tianjin Municipality, 300020

  • Tianjin Medical University General Hospital

    Tianjin, Tianjin Municipality, 300052

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

    Wuhan, Hubei, 430022

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

    Xi’an, Shanxi, 710004

  • The First Affiliated Hospital of Xiamen University

    Xiamen, Fujian, 361003

  • Henan Cancer Hospital

    Zhengzhou, Henan, 450008

Other trials in China

About this study

Official title: A Multicenter, Open-label, Phase 1/2a 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)

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.

Being tested
TJ011133
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TJ011133Drug

    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.

Study groups in NCT04202003
Study groupRoleWhat they receive
TJ011133ExperimentalThis 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.
Receives: Drug: TJ011133

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose Limiting Toxicities(DLT)

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

    Measured: 28days after first dose

  2. 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.

    Measured: Through study completion, an average of 1 year

  3. Recommended phase II dose

    Recommended phase II dose (RP2D)

    Measured: Through study completion, an average of 1 year

  4. 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

    Measured: Through study completion，an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2019
  2. Study start25 Mar 2020
  3. Primary completion15 Dec 2023
  4. Study completion15 Dec 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
105 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04202003
Sponsor's protocol ID
TJ011133AML102
Status last verified
Apr 2024
First submitted
13 Dec 2019
Last updated
15 Apr 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing TJ011133 in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes(MDS), run by TJ Biopharma Co., Ltd. at 26 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 38 inclusion and 39 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose Limiting Toxicities(DLT) (time frame: 28days after first dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04202003.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Apr 2024.

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