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

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ClinicalTrials.gov Identifier: NCT03974243
Recruitment Status : Not yet recruiting
First Posted : June 4, 2019
Last Update Posted : June 4, 2019
Sponsor:
Information provided by (Responsible Party):
Chipscreen Biosciences, Ltd.

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.

Condition or disease Intervention/treatment Phase
Non-hodgkin's Lymphoma Drug: Chiauranib Drug: Chidamide Phase 1 Phase 2

Detailed Description:

The purpose of this study is to assess the tolerability and safety include adverse events, vital signs, laboratory tests ,etc., of a range of doses of Chiauranib and Chidamide in patients with relapsed or refractory non-Hodgkin's lymphoma, and to determine the dose limit toxicity and the maximum tolerable dose.

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib/IIa Study of Chiauranib in Combination With Chidamide in Patients With Relapsed/Refractory Non-Hodgkin's Lymphoma
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : March 2021
Estimated Study Completion Date : September 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: treatment group

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

Intervention: Drug: Chiauranib and Chidamide

Drug: Chiauranib

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.

Other Name: CS2164

Drug: Chidamide
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
Other Name: CS055




Primary Outcome Measures :
  1. dose-limiting toxicity (DLT) [ Time Frame: Day 1 - 28 ]

Secondary Outcome Measures :
  1. Area under the concentration versus time curve (AUC) [ Time Frame: Day 1 of the lead-in period and Day 1 of the combination therapy ]
    pharmacokinetic profile of Chiauranib in combination with Chidamide

  2. Peak plasma concentration (Cmax) [ Time Frame: Day 1 of the lead-in period and Day 1 of the combination therapy ]
    pharmacokinetic profile of Chiauranib in combination with Chidamide

  3. Time of Cmax (Tmax) [ Time Frame: Day 1 of the lead-in period and Day 1 of the combination therapy ]
    pharmacokinetic profile of Chiauranib in combination with Chidamide

  4. Objective response rate [ Time Frame: About 21 weeks ]
  5. complete response rate [ Time Frame: About 21 weeks ]
  6. disease control rate [ Time Frame: About 21 weeks ]
  7. time to progression [ Time Frame: About 21 weeks ]
    duration from date of treatment until the date of first documented progression

  8. Progression free survival [ Time Frame: About 21 weeks ]
    From date of treatment until the date of first documented progression or date of death from any cause, whichever came first

  9. Duration of response [ Time Frame: About 21 weeks ]
    From the first date of response until the date of first documented progression

  10. Adverse events [ Time Frame: About 21 weeks ]
    Number of participants with treatment-related adverse events according to CTCAE V4.03

  11. Any single mutation of oncogene and copy number variation in ctDNA(single gene analysis) [ Time Frame: day -1 of therapy ]
  12. Mutation of polygene and copy number variation in signal pathway(multi-gene analysis) [ Time Frame: day -1 of therapy ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or Female, aged ≥ 18 yrs and ≤70 yrs;
  2. Patients with NHL refractory to at least 2 different chemotherapies , for which no standard therapy exists;
  3. At least 1 lesion can be accurately measured, as defined by Lugano 2014 criteria.
  4. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1;
  5. 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;
  6. 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

  7. Life expectancy of at least 3 months.
  8. Willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Clinical evidence of central nervous system involvement
  2. 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;
  3. Previous treatment with HDAC inhibitors(include Chidamide) or aurora kinase(include Chiauranib) inhibitors;
  4. 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;
  5. Have active bleeding current thrombotic disease, patients with bleeding potential ,or receiving anticoagulation therapy; within 2 months prior to screening;
  6. Proteinuria positive(≥1g/24h);
  7. History of deep vein thrombosis or pulmonary embolism;
  8. Have unsolved toxicities (> grade 1) from prior anti-cancer therapy;
  9. 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;
  10. History of organ transplantation ,Allogeneic bone marrow transplantation or autologous stem cell transplantation;
  11. High-risk surgery for vital organs within 6 weeks prior to screening or the investigators determined that other surgical wounds did not heal well;
  12. Serologically positive for HIV, hepatitis B or C, or other serious infectious diseases;
  13. History of interstitial lung disease(ILD);
  14. Any mental or cognitive disorder, that would impair the ability to understand the informed consent document or the operation and compliance of study;
  15. Candidate with drug and alcohol abuse;
  16. 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);
  17. Any other condition which is inappropriate for the study in the opinion of the investigators.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03974243


Locations
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China, Beijing
Beijing Cancer Hospital
Beijing, Beijing, China
Sponsors and Collaborators
Chipscreen Biosciences, Ltd.

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Responsible Party: Chipscreen Biosciences, Ltd.
ClinicalTrials.gov Identifier: NCT03974243     History of Changes
Other Study ID Numbers: CAR106
First Posted: June 4, 2019    Key Record Dates
Last Update Posted: June 4, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases