Chiauranib in Combination With Chidamide in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma

NCT03974243 | Completed Phase 1

• 1 other identifier: CAR106
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this dose-escalation study is to assess the safety and tolerability of treatment with Chiauranib and Chidamide administered orally over a range of doses in patients with relapsed or refractory non-Hodgkin's lymphoma, in the meantime, exploring the pharmacodynamic profile and latent biomarkers accompany with Chiauranib and Chidamide , as well as the relevancy of which and clinical benefit.

Conditions

Non-hodgkin's Lymphoma

Outcome Measures

Primary Outcomes (1)

• dose-limiting toxicity (DLT)

  Day 1 - 28

Secondary Outcomes (12)

• Area under the concentration versus time curve (AUC)

  Day 1 of the lead-in period and Day 1 of the combination therapy

• Peak plasma concentration (Cmax)

  Day 1 of the lead-in period and Day 1 of the combination therapy

• Time of Cmax (Tmax)

  Day 1 of the lead-in period and Day 1 of the combination therapy

• Objective response rate

  About 21 weeks

• complete response rate

  About 21 weeks

Study Arms (1)

treatment group

EXPERIMENTAL

In this arm, patients would be given the regimen composed of Chiauranib and Chidamide orally. Intervention: Drug: Chiauranib and Chidamide

Drug: Chiauranib; Drug: Chidamide

Interventions

Chiauranib DRUG

In the lead-in period, patients take 50mg Chiauranib capsules on the forth day . In the subsequent treatment cycles, Chiauranib capsules are given orally once daily, 28 days as a cycle.

Also known as: CS2164

treatment group

Chidamide DRUG

In the lead-in period, patients take a single dose of Chidamide tablet on the first day and then off for 3 days before the first cycle begins. In the subsequent treatment cycles, Chidamide tablets are given orally on Day 1,4,8,11,15,18,22 and 25 of each cycle. 28 days as a cycle

Also known as: CS055

treatment group

Eligibility Criteria

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

You may qualify if:

• Male or Female, aged ≥ 18 yrs and ≤70 yrs;
• Patients with NHL refractory to at least 2 different chemotherapies , for which no standard therapy exists;
• At least 1 lesion can be accurately measured, as defined by Lugano 2014 criteria.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
• 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;
• 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
• Life expectancy of at least 3 months.
• Willingness to sign a written informed consent document.

You may not qualify if:

• Clinical evidence of central nervous system involvement
• 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;
• Previous treatment with HDAC inhibitors(include Chidamide) or aurora kinase(include Chiauranib) inhibitors;
• Have uncontrolled or significant cardiovascular disease, including:
• 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.
• primary cardiomyopathy(dilated cardiomyopathy, hypertrophic cardiomyocyte, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, et,al)
• History of significant QT interval prolongation, or Corrected QT Interval (QTc) \> 450 ms prior to study entry
• Symptomatic coronary heart disease requiring treatment with agents
• Uncontrolled hypertension (\> 140/90 mmHg) by single agent;
• Have active bleeding current thrombotic disease, patients with bleeding potential ,or receiving anticoagulation therapy; within 2 months prior to screening;
• Proteinuria positive(≥1g/24h);
• History of deep vein thrombosis or pulmonary embolism;
• Have unsolved toxicities (\> grade 1) from prior anti-cancer therapy;
• 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;
• History of organ transplantation ，Allogeneic bone marrow transplantation or autologous stem cell transplantation;

Sponsors & Collaborators

• Chipscreen Biosciences, Ltd.: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

chiauranib; N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System 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: May 30, 2019
• First Posted: June 4, 2019
• Study Start: July 11, 2019
• Primary Completion: December 31, 2021
• Study Completion: December 31, 2021
• Last Updated: March 9, 2022

Record last verified: 2021-08

Locations

CN (1)