Clinical trial NCT02809573: Clinical Trial of Chidamide Combined With CHOP in Peripheral T-cell Lymphoma Patients
Official title: An Open-label, Multi-center, Phase Ib Clinical Trial of Chidamide Combined With CHOP in Newly Diagnosed Peripheral T-cell Lymphoma Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Peripheral T-cell Lymphoma
Keywords: peripheral T-cell lymphoma
PTCL
chidamide
CHOP
phase Ib
Lead sponsor: Chipscreen Biosciences, Ltd.
Sponsor class: INDUSTRY
First posted: 2016-06-22
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this dose-escalation study is to assess the safety and tolerability of treatment with Chidamide in a range of doses combined with CHOP in fixed dose in patients with newly diagnosed peripheral T-cell lymphoma.

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 chidamide combined with CHOP in peripheral T-cell lymphoma patients, and to determine the dose limit toxicity and the maximum tolerable dose.

Eligibility criteria: Inclusion Criteria:

1. Male and female aged 18-65 years old;
2. Histopathologically confirmed Peripheral T -cell Lymphoma (PTCL) including:

   * PTCL-unspecified;
   * Angioimmunoblastic T-cell lymphoma;
   * Anaplastic large cell lymphoma, ALK positive or negative;
   * Subcutaneous panniculitis T-cell lymphoma;
   * Cutaneous / T-cell lymphoma;
   * Other T-cell lymphoma that investigators consider to be appropriate to be enrolled;
3. Patients have not received anti-tumor therapy;
4. In any Ann Arbor disease stage;
5. ECOG performance status 0-1;
6. Patients without bone marrow involvement. The absolute number of neutrophile is no less then 2.0 \* 10\^9/L, platelet no less then 100 \* 10\^9/L. And the concentration of hemoglobin is no less than 110 g/L;
7. Life expectancy is no less than 6 months;
8. Patients who have signed the Informed Consent Form.

Exclusion Criteria:

1. Patients who have central nervous system or meninges involvements;
2. Patients have been treated by radiotherapy, chemotherapy or immunotherapy for PTCL;
3. Patients have uncontrollable or significant cardiovascular disease including:

   * history of myocardial infarction;
   * uncontrollable angina within the 6 months before screening, or taking anti-angina drugs at the time of screening;
   * history of congestive heart failure, or the left ventricular ejection fraction (LVEF) is \< 50% at the time of screening;
   * clinically significant ventricular arrhythmia such as ventricular tachycardia, ventricular fibrillation or torsades de pointes;
   * History of supraventricular arrhythmia or nodal arrhythmia that could not been controlled by drug or need a pacemaker;
   * History of cardiomyopathy;
   * History of clinically significant QTc interval prolongation, or QTc interval \> 450 ms at screening;
   * Coronary disease which is with symptoms and needs drug therapy;
4. Patients have undergone organ transplantation;
5. Patients with thromboembolic disease, hematencephalon or cerebral infraction within 4 weeks before screening, or patients who are under anticoagulant therapy;
6. Patients with clinically significant abnormalities in gastrointestinal tract, such as dysphagia, chronic diarrhea and intestinal obstruction which may affect the uptake,transformation and absorption of the drug;
7. Patients with active infections, including active bacterial,viral,fungoid, mycobacterium, parasite infections (but not including hyponychium fungoid infection), or infections which need not be treated by intravenous antibody therapies, or antiviral therapies, or any serious infection need to be treated by hospitalization;
8. Patients who have been conducted the surgery on a major organ in less than 6 weeks;
9. Hepatic function: Serum total bilirubin \> 1.5 fold of normal range; ALT/AST \> 2.5 folds of normal range or 5 folds for liver metastasis; Renal function: Serum creatine \> 1.5 folds of normal range;
10. Patients with other malignancies in the past or now (except basal cell carcinoma, squamous-cell carcinoma or carcinoma in situs of cervix that has been adequately treated),unless the malignancy has been radically treated and there has been no evidence of recurrence for 5 years;
11. Pregnant or lactating women and patients in childbearing age who will not carry out birth control;
12. Patients with mental disorders, which may affect understanding and execution of informed consent or the compliance of the study;
13. Drug abuse or long term alcoholism that could affect the evaluation for the study results;
14. Patients considered by investigators not suitable for the study.

Primary outcomes:
measure: dose-limiting toxicity (DLT)
timeFrame: Day 1 - 21
Secondary outcomes:
measure: Adverse events
timeFrame: About 21 weeks
measure: complete response rate
timeFrame: About 21 weeks
measure: Duration of response
timeFrame: About 21 weeks
measure: Progression free survival
timeFrame: About 21 weeks
measure: Objective response rate
timeFrame: About 21 weeks
measure: Overall survival
timeFrame: About 21 weeks
measure: Area under the concentration versus time curve (AUC)
timeFrame: Day 1 of the lead-in period and Day 1 of the combination therapy
measure: Peak plasma concentration (Cmax)
timeFrame: Day 1 of the lead-in period and Day 1 of the combination therapy
measure: Time of Cmax (Tmax)
timeFrame: Day 1 of the lead-in period and Day 1 of the combination therapy
Other outcomes:
Locations:
city: Beijing
country: China
facility: Cancer Hospital, Chinese Academy of Medical Sciences
state: Beijing
Study officials:
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
name: Yuankai Shi, MD
role: PRINCIPAL_INVESTIGATOR
References: