Study of Chiauranib in Relapsed/Refractory Non-Hodgkin's Lymphoma

Efficacy and Safety of Chiauranib in Relapsed/Refractory Non-Hodgkin's Lymphoma: a Single-arm, Open-label, Multi-site, Exploratory Phase Ib Study

Chiauranib may stop the growth of tumor cells by blocking Aurora kinase B（Aurora B）、VEGFR/PDGFR/c-Kit、CSF-1R targets.

This clinical trial is studying the efficacy and safety of chiauranib works in treating patients with relapsed or refractory non-Hodgkin's lymphoma, in the meantime, exploring the latent biomarkers accompany with chiauranib, as well as the relevancy of which and clinical benefit.

Study Overview

• Status: Terminated
• Conditions: Non-Hodgkin's Lymphoma
• Intervention / Treatment: Drug: Chiauranib

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100021
      • Cancer Hospital, Chinese Academy of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or Female, aged ≥ 18 yrs and ≤70 yrs;
2. Histological or cytological confirmation of non-Hodgkin's lymphoma（NHL）, including diffuse large B-cell lymphoma, peripheral T-cell lymphoma and other aggressive NHLs which determined by the investigator.
3. Patients with NHL refractory to at least 2 different chemotherapies , for which no standard therapy exists;
4. At least 1 lesion can be accurately measured, as defined by Lugano 2014 criteria.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
6. Subjects received anti-cancer therapy (including chemotherapy, radiotherapy, immunotherapy and surgical therapy, et al) should beyond 4 weeks prior to study entry; Subjects received mitomycin chemotherapy should beyond 6 weeks prior to study entry; Subjects received autologous stem cell transplantation should beyond 3 months prior to study entry;

7. Laboratory criteria are as follows:

   Complete blood count: hemoglobin (Hb) ≥90g/L ; absolute neutrophil count (ANC) ≥1.5×109/L ; platelets >=90×109/L Biochemistry test: total bilirubin≦1.5×ULN; alanine aminotransferase(ALT) ,aspartate aminotransferase(AST)≦1.5×ULN; (ALT,AST≦5×ULN if liver involved) ;serum creatinine(cr)≦1.5×ULN; Coagulation test: International Normalized Ratio (INR) < 1.5

8. Life expectancy of at least 12 weeks.
9. Willingness to sign a written informed consent document.

Exclusion Criteria:

1. Patients with prior invasive malignancies with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, unless received curative treatment and with documented evidence of no recurrence in the past five years;
2. Clinical evidence of central nervous system involvement;

3. Have uncontrolled or significant cardiovascular disease, including:

   1. Congestive heart failure, unstable angina pectoris, myocardial infarction within 6 months prior to study entry; arrhythmia, or Left Ventricular Ejection Fraction (LVEF) < 50% requiring treatment with agents during screening stage.
   2. primary cardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al)
   3. History of significant QT interval prolongation, or Corrected QT Interval (QTc) > 450 ms prior to study entry
   4. Symptomatic coronary heart disease requiring treatment with agents
   5. Uncontrolled hypertension (> 140/90 mmHg) by single agent;
4. Have active bleeding current thrombotic disease, patients with bleeding potential ,or receiving anticoagulation therapy; within 2 months prior to screening;
5. Proteinuria positive(≥1g/24h);
6. History of deep vein thrombosis or pulmonary embolism;
7. Have unsolved toxicities (> grade 1) from prior anti-cancer therapy;
8. Have clinical significant gastrointestinal abnormality, e.g., unable to swallow, chronic diarrhea, ileus, that would impair the ingestion,transportation or absorption of oral agents, or patients undergone gastrectomy;
9. History of organ transplantation or Allogeneic bone marrow transplantation;
10. Major surgery within 6 weeks and minor surgery within 2 weeks prior to screening (excluding placement of vascular access or biopsy) that involved general anaesthesia or respiratory assistance;
11. Serologically positive for HIV, hepatitis B or C, or other serious infectious diseases;
12. History of interstitial lung disease(ILD);
13. Previous treatment with aurora kinase inhibitors;
14. Patients appropriate and ready for autologous stem cell transplantation;
15. Any mental or cognitive disorder, that would impair the ability to understand the informed consent document or the operation and compliance of study;
16. Candidate with drug and alcohol abuse;
17. Participants of reproductive potential not willing to use adequate contraceptive measures for the duration of the study (both male and female participants).Pregnant or breastfeeding women. Female participants must have a negative urinary or serum pregnancy test when done or have evidence of post-menopausal status (Defined as absence of menstruation for greater than 12 months, bilateral oophorectomy or hysterectomy);
18. Any other condition which is inappropriate for the study in the opinion of the investigators.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: chiauranib; Patients take Chiauranib capsules 50mg, orally once daily, 28 days as a cycle.	Drug: Chiauranib; Take 50mg orally once daily; Other Names: CS2164

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate(ORR)	ORR will be calculated from the data obtained from the end visit	assessed up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
duration of response (DOR)	From the first date of response until the date of first documented progression	assessed up to 2 years
Number of participants with treatment-related adverse events	measured by adverse events (AE), serious adverse events (SAE), abnormal vital signs，electrocardiograph(ECG) and abnormal laboratory results according to CTCAE V4.03	Measured through 2 years
progression-free survival (PFS)	From date of treatment until the date of first documented progression or date of death from any cause, whichever came first	assessed up to 2 years
time to progression(TTP)	duration from date of treatment until the date of first documented progression	through treatment completion, up to 2 years
complete remission rate(CRR)		through treatment completion, up to 2 years
overall survival(OS)	Time from treatment to death from any cause	assessed up to 2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
immunohistochemical(IHC) staining results of Aurora B、CSF-1R and Myc protein	The IHC staining results were assigned a mean follows: 0, negative; 1, weak; 2, moderate; and 3, strong. The frequency of positive cells was defined as follows: 0, less than 5%; 1, 5% to 25%; 2, 26% to 50%; 3, 51% to 75%; and 4,greater than 75%.	assessed up to 2 years
Any single mutation of oncogene and copy number variation in ctDNA(single gene analysis)		assessed up to 2 years
Mutation of polygene and copy number variation in signal pathway(multi-gene analysis)		assessed up to 2 years

Collaborators and Investigators

• Sponsor: Chipscreen Biosciences, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): May 9, 2017
• Primary Completion (Actual): August 15, 2017
• Study Completion (Actual): February 14, 2019

Study Registration Dates

• First Submitted: March 1, 2017
• First Submitted That Met QC Criteria: March 5, 2017
• First Posted (Actual): March 9, 2017

Study Record Updates

• Last Update Posted (Actual): July 24, 2019
• Last Update Submitted That Met QC Criteria: July 22, 2019
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: Non-Hodgkin's lymphoma; Relapsed/Refractory; Aurora kinase B
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Chiauranib
• Other Study ID Numbers: CAR103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No