Safety, Tolerability and PK of BTK Inhibitor DTRMWXHS-12 in Patients With B-Cell Lymphomas

• Status: Completed
• Trial end date: 2019-02-01
• Target enrollment: 0
• Participant gender: All

Summary

The Primary Objective is to evaluate the safety and tolerability of multiple dose oral administration of DTRMWXHS-12 capsule in patients with B-cell lymphoma.

The Secondary Objective is to evaluate the pharmacokinetics of multiple dose oral administration of DTRMWXHS-12 capsule in patients with B-cell lymphoma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Zhejiang DTRM Biopharma

Criteria

Inclusion Criteria:

• Age≥18 years, gender is not limited. Patients are voluntary to sign the informed consent form.

• B-Cell Lymphoma based on WHO classified definition: including chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL); chronic lymphocytic leukemia with 17p-; mantle cell lymphoma (MCL); Waldenstrom's macroglobulinemia(WM); Diffuse large B-cell lymphoma (DLBL or DLBCL) etc.

• Measurable lesion: non-Hodgkin 's lymphoma requires at least a two-dimensional lesion diameter ≥ 2 cm, chronic lymphocytic leukemia ≥ 5000 leukemia cells / mm3, Waldenstrom's macroglobulinemia IgM ≥ 1000 mg / dL, bone marrow lymph plasma -like cells infiltration, Histopathologically diagnosed as Diffuse Large B- Cell Lymphoma.

• Investigator judges that the treatment is needed.

• Patients, who at least failed in lymphoma treatment once and without standard therapeutic options, can't satisfy the requirement or decline treatment or failed in autologous stem cell transplantation for Diffuse Large B- Cell Lymphoma.

• ECOG (Eastern Cooperative Oncology Group) performance status 0 ~1

• Life expectancy greater than 4 months

• Ability to swallow capsules

• Hematologic functions satisfy: Neutrophils ≥1.5×109 / L ( according to the investigators' opinion , if they judge that the patients' neutrophil count lower than this threshold, which caused by chronic lymphocytic leukemia and bone marrow infiltration, those patients are eligible to be included. ), platelet(PLT) ≥75×109/L, HB≥80g/L

• Renal functions satisfy: Creatinine (Cr) ≤ 1.5 times of upper limit of normal persons; creatinine clearance rate≥50ml/min (estimated by Cockcroft-Gault formula or detected by nuclear medicine scan or 24 hours urine method)

• Liver functions satisfy: AST and ALT≤2.5 times of normal value, bilirubin ≤1.5 times of normal value

• Coagulation function: international normalized ratio (INR) and APTT ≤ 1.5 times of normal value;

• Throughout the course of the study and 90 days of treatment interruption, female of childbearing age and fertile males who must take one of the following effective contraception measures: abstinence, barrier-type dual contraceptive methods, IUDs, administration of hormonal contraception drug.

• Male subjects are prohibited sperm donation from the start to the end of treatment within 90 days.

Exclusion Criteria:

• Patients with brain metastasis

• Disease with changes of pathological tissue types (including large cell transformation)

• Patients who received allogeneic stem cell transplantation within 6 months, or with organized incompatibility reaction (GVHD), requires immunosuppressive therapy

• Patients who received steroid anti-tumor therapy within 7 days, or receive chemotherapy within 2 weeks, or receive monoclonal antibody therapy within 4 weeks, prior to first administration of DTRMWXHS-12 capsule.

• Patients received other BTK inhibitor therapy

• Patients had early received chemotherapy but their toxicity has not been cleared (according to NCI-CTCAE 4.03, unrecovered toxicity grade ≤1)

• Patients who received Chinese herbal anti-tumor therapy within 1 week before the start of study

• Patient with a history of other malignant within 2 years before enrollment, except (1) adequately treated in situ cervical cancer;(2) Local basal cell carcinoma or squamous cell carcinoma (3) Local malignant tumor which has been completely treated (by surgery or other means)

• Patients with uncontrolled systemic infection requiring intravenous anti-infection treatment

• Patients received major surgery in the past 4 weeks

• Patients with HIV infection, HBs-Ag positive

• According to New York Heart Association (NYHA) classification, patients with cardiovascular disease of grade ≥3

• Patients with history of Myocardial infarction, acute coronary syndrome (unstable angina), receiving coronary angioplasty and stent implantation within 6 months of study entry

• Patients applied something which may cause QT prolongation or accompany by torsades healer within 7 days prior to enrollment.

• Prolonged QTc interval (defined as a QTc> 450 ms) or other significant ECG abnormalities, including second degree atrioventricular block type Ⅱ, third degree atrioventricular block, or bradycardia (heart rate less than 50 beats / min),ECG QTc> 450 milliseconds, the ECG may be submitted to expert for centralized evaluation

• Subjects, the investigators think whose existing renal disease, neurological / psychiatric disorders, liver or endocrine disorders could affect their participating in the experiment

• Subjects with poor compliance

• Subjects are using CYP3A inhibitors (or inducer)