Relapsed or Refractory Lymphoma
Conditions
Interventions
1:10 mg BID x 5 days
2:20mg mane & 10mg nocte x 5 days
3:20mg BID x 5 days
Sponsors
Queen Mary Hospital, The University of Hong Kong
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Chinese male or female subject; 2. Aged >=18 years at the time of signing informed consent; 3. Histologically or cytologically confirmed relapsed/refractory lymphoma with the potential to benefit from HDAC inhibitor therapy; 4. At least one measurable lesion as defined by Lugano classification (Cheson et al. 2014). Measurable lesion is defined as, bi-dimensionally measurable nodal lesion with at least 1.5 cm in its longest dimension, or bi-dimensionally measurable extranodal lesion with size at least 1.0 cm in its longest dimension; 5. Adequate bone marrow function at screening and pre-dose: (1) Hemoglobin >=10 g/dl; (2) Absolute neutrophil count (ANC) > 1.5x10^9/L; (3) Platelet count >=75x10^9/L; (4) PT-INR <1.5 or APTT <1.5 ULN; 6. Adequate liver function at screening and pre-dose: (1) Total bilirubin < 1.25 ULN; (2) Serum AST and ALT < 2.5 ULN; (3) Serum ALP < 2.5 ULN; 7. Adequate renal function at screening and pre-dose: serum creatinine <1.25 ULN; 8. Life expectancy of at least 12 weeks; 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; 10. Patients are suitable for and willing to receive a tumour biopsy, or adequate archived tumour sample (obtained within 3 months prior to starting of first dosing) is available for processing of HR23B expression; 11. Female patients with childbearing potential (including female subjects who are within 12 months of menopause) must agree to use a medically acceptable method of contraception throughout the treatment period and for 16 weeks after discontinuation of treatment. (Acceptable contraceptive methods include abstinence for at least 1 month prior to screening, correct use of condom, spermicides, injectables/combined oral contraceptives, intra-uterine device with or without local hormone release, cervical cap or diaphragm and vasectomy performed at least 1 year prior to screening); 12. Male patients who have partners of childbearing potential or whose partners are pregnant must use acceptable contraception throughout the treatment period and for 16 weeks after discontinuation of treatment; 13. Patients is willing and able to comply with drug-taking instruction, scheduled study visits, study procedures and examinations; 14. Able to understand the nature, scope and possible consequences of participation in the study; 15. Willing and able to provide a written informed consent.
Exclusion criteria
Exclusion criteria: 1. Patients who have received any anti-cancer therapy including radiotherapy (except for palliative reasons), endocrine therapy, immunotherapy or use of other investigational agents within 28 days prior to first dosing of study drug. Limited field radiotherapy to an isolated lesion in bone or soft tissue must be completed 14 days prior to the first dosing of the study drug; (Patients may continue the use of bisphosphonates for bone disease or corticosteroids providing the dose is stable before the trial); 2. Any known brain metastases, unless these are shown to be stable (symptomatically and/or radiologically) over a period of 2 months or more; 3. Any toxic effects (except hair loss) of the prior therapy have not been resolved to Grade 1 or less according to CTCAE v.4.03; 4. Any major surgery within 4 weeks prior to the first dosing of the study drug; 5. Co-existing active infection requiring parenteral antibiotics or serious concurrent illness deemed clinically significant within 4 weeks prior to the first dosing of the study drug.; 6. Patients who are known to be serologically positive for human immunodeficiency viruses (HIV), or seropositive results consistent with active hepatitis B virus or active hepatitis C virus infection (Chronic hepatitis B carriers on anti-viral therapy and with HBV DNA level =450msec measured at screening; 10. Previous treatment with a HDAC inhibitor; 11. Female patients who have positive pregnancy test at Screening and/or pre-dose Day 1, planning to become pregnant during the study until 16 weeks after the last dose of the study treatment; 12. Female patients who are lactating; 13. Any condition that is unstable or can jeopardize the safety of the patients and their compliance to the study. 14. HIV ab positive, HCV ab positive, and HBsAg positive with DNA copies >=1000 copies/ml.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1) Incidence and severity of adverse events (AEs)- event severity will be graded according to CTCAE version 4.03.;MTD; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters of single-dose & multiple-dose CXD101;PD biomarkers;ORR;DOR;DCR;PFS;4) Relationship of tissue expression of HR23B with tumour response to CXD101;OS; | — |
Countries
China
Contacts
Public ContactKWONG Yok Lam
Department of Haematology and Haematological Oncology, Queen Mary Hospital, The University of Hong Kong
Outcome results
None listed