A Phase Ib Study of CT053PTSA in Relapsed / Refractory Acute Myeloid Leukemia (AML)

NCT03125876 | Terminated Phase 1

• 1 other identifier: PCD-DCT053-16-002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of CT053PTSA in Relapsed/refractory AML patients with FLT3 gene mutation.

Conditions

Acute Myeloid Leukemia (AML)

Outcome Measures

Primary Outcomes (1)

• Maximum tolerated dose (MTD)

  Safety and Tolerability assessed through adverse events to determine maximum tolerated dose

  day 1-28

Secondary Outcomes (4)

• Maximum observed plasma concentration (Cmax)

  On day 1,8,15,22,29

• Time of maximum observed plasma concentration (Tmax)

  On day 1,8,15,22,29

• Area under the plasma concentration time curve

  On day 1,8,15,22,29

• Objective response rate (ORR)

  Through study completion, an expected average of 1.5 year

Study Arms (1)

CT053PTSA

EXPERIMENTAL

60mg-100mg

Drug: CT053PTSA

Interventions

CT053PTSA DRUG

receive oral CT053PTSA once daily until disease progression or unacceptable toxicity occurs, each cycle is defined as 28 days

Also known as: Ningetinib

CT053PTSA

Eligibility Criteria

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

You may qualify if:

• study population
• a) documented acute myeloid leukemia according to World Health Organization（WHO） criteria(excluding acute promyelocytic leukemia), with Fms-like Tyrosine Kinase 3 (FLT3) gene mutation,refractory/relapsed after common or enhanced chemotherapy c) Recovered from toxicity of previous treatment d) Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 e) Life expectation ≥ 12 weeks
• Subjects must have adequate organ function and meeting all of the following laboratory review before enrollment a)blood routine examination: WBC≤2000/mm3 b)liver function: Alanine aminotransferase (ALT) and Aspartate transaminase (AST) ≤2.5×upper limit of normal(ULN); serum bilirubin ≤ 1.5 × ULN c)renal function: Serum creatinine ≤ 1.5×ULN, or the creatinine clearance (CrCl)≥ 60 mL / min calculated by the Cockcroft-Gault formula d) electrolyte: serum potassium≥3.0mmol/L; serum calcium≥2.0 mmol/L e) abnormal serum amylase without symptom≤1.5 × ULN; serum Lipase ≤1.5× ULN f) coagulation function:fibrinogen≥1.0g/L; activated partial thromboplastin time( APTT)≦ULN+10s; prothrombin time(PT)≤ULN+3s g) no obvious organ dysfunction 3)subjects must volunteer to provide evidence of effective diagnosis prior to entry or to accept bone marrow puncture or biopsy for diagnosis, and accept bone marrow puncture or biopsy after treatment to evaluate the efficacy 4) Sign the informed consent

You may not qualify if:

• Subject meeting any of the following criteria will be excluded.
• treatment history
• chemotherapy, immunotherapy, radiotherapy, or major surgery within 4 weeks prior to administration;
• nitrosourea and mitomycin chemotherapy within 6 weeks prior to the administration;
• have taken live vaccines within 4 weeks prior to /or concurrent with the administration;
• received FLT3 or Axl inhibitors within 6 weeks prior to the administration;
• have received a trial investigational product, or participated in other clinical trials within 4 weeks prior to administration
• disease history and surgery history
• a) documented promyelocytic leukemia (t (15; 17) (q22; q11) and / or promyelocytic leukemia(PML)/retinoic acid receptor alpha (RARa) positivity found in the chromosome, variant acute promyelocytic leukemia) b) with myeloid sarcoma or invasion of central nervous system; c) high blood pressure and not well controlled by drug (blood pressure ≥ 140/90 mmHg). Note: Blood pressure before the first administration (mean blood pressure of two measures that 24 hours interval or above ) should be controlled within 140/90 mmHg.
• d) Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) \<50%; e) NCI CTCAE 4.03 ≥ 2 grade of arrhythmia, or corrected QT interval(QTc )\> 450 ms ; patients with a history of torsion or congenital QT prolonged syndrome; f) any of the illness bellowed within 12 months prior to administration: myocardial infarction, severe or unstable angina, coronary artery bypass graft or peripheral artery bypass surgery, congestive heart failure, cerebrovascular events (including Transient ischemic attack); g) multiple factors that affect oral medication (eg, can not swallow, chronic diarrhea and intestinal obstruction, etc.); h)obvious tendency of gastrointestinal bleeding, including the following cases: local active ulcer lesion, and fecal occult blood test(≥++); melena or hematemesis within 2 months; gastrointestinal bleeding may occurs considered by investigator.
• i)history of immunodeficiency, other acquired or congenital immunodeficiency,history of organ transplantation; j) previous thyroid dysfunction,thyroid function can not be maintained at the normal range even have drug taken.
• k)Human immunodeficiency virus(HIV) positivity l) Hepatitis B surface antigen (HBsAg)positivity, and in the active phase(hepatitis B nucleic acid quantity≥ 1.00 × 103copies / ml); m) Hepatitis C antibody(Anti-HCV) positivity and in the active phase (hepatitis C nucleic acid quantity ≥1.00 × 102copies / ml) n) severe retinopathy or exfoliation judged by the Investigator; o) severe electrolyte imbalance judged by the investigator; p) active infectious disease judged by the investigator; q) other acute or chronic medical or psychological illnesses that are not suitable for clinical trials considered by the investigator or sponsor;
• Pregnant or lactating women or female and male with fertility plan. 4)the therapy and/or drug forbidden
• taking anticoagulant or vitamin K antagonist such as warfarin, heparin or other similar drugs;
• taking other anti-leukemia drugs at the same time, including traditional Chinese medicine (some Chinese medicine can not be used listed in Annex 4);

Sponsors & Collaborators

• Sunshine Lake Pharma Co., Ltd.: lead

Study Sites (1)

Hospital of Blood Disease, Chinese Academy of Medical Sciences

Tianjin, China

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

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

Study Officials

• Jianxiang Wang, Doctor

  Hospital of Blood Disease, Chinese Academy of Medical Sciences

  STUDY CHAIR

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: April 9, 2017
• First Posted: April 24, 2017
• Study Start: November 13, 2017
• Primary Completion: August 19, 2019
• Study Completion: August 19, 2019
• Last Updated: March 24, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)