Safety, Tolerability and PK of BTK Inhibitor DTRMWXHS-12 in Patients With B-Cell Lymphomas
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: DTRMWXHS-12 DTRMWXHS-12 only: oral capsules (50 mg and 150 mg strengths), successive administration, dose escalation from 50mg to 100, 200, 400, 600, 800mg daily until MTD. During successive administration, orally once a day, 28 days as a cycle. |
Drug: DTRMWXHS-12
|
Outcome Measures
Primary Outcome Measures
- Number of participants with adverse events [Starting from date of first dose up to 30 days after last dose]
Confirm the safety and tolerability of multiple dose oral administration of DTRMWXHS-12 capsule
Secondary Outcome Measures
- Plasma concentrations of DTRMWXHS-12 [Days 1-28 (first treatment cycle)]
DTRMWXHS-12 Pharmacokinetics
Eligibility Criteria
Criteria
Inclusion Criteria:
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Age≥18 years, gender is not limited. Patients are voluntary to sign the informed consent form.
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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.
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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.
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Investigator judges that the treatment is needed.
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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.
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ECOG (Eastern Cooperative Oncology Group) performance status 0 ~1
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Life expectancy greater than 4 months
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Ability to swallow capsules
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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
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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)
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Liver functions satisfy: AST and ALT≤2.5 times of normal value, bilirubin ≤1.5 times of normal value
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Coagulation function: international normalized ratio (INR) and APTT ≤ 1.5 times of normal value;
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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.
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Male subjects are prohibited sperm donation from the start to the end of treatment within 90 days.
Exclusion Criteria:
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Patients with brain metastasis
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Disease with changes of pathological tissue types (including large cell transformation)
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Patients who received allogeneic stem cell transplantation within 6 months, or with organized incompatibility reaction (GVHD), requires immunosuppressive therapy
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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.
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Patients received other BTK inhibitor therapy
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Patients had early received chemotherapy but their toxicity has not been cleared (according to NCI-CTCAE 4.03, unrecovered toxicity grade ≤1)
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Patients who received Chinese herbal anti-tumor therapy within 1 week before the start of study
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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)
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Patients with uncontrolled systemic infection requiring intravenous anti-infection treatment
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Patients received major surgery in the past 4 weeks
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Patients with HIV infection, HBs-Ag positive
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According to New York Heart Association (NYHA) classification, patients with cardiovascular disease of grade ≥3
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Patients with history of Myocardial infarction, acute coronary syndrome (unstable angina), receiving coronary angioplasty and stent implantation within 6 months of study entry
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Patients applied something which may cause QT prolongation or accompany by torsades healer within 7 days prior to enrollment.
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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
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Subjects, the investigators think whose existing renal disease, neurological / psychiatric disorders, liver or endocrine disorders could affect their participating in the experiment
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Subjects with poor compliance
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Subjects are using CYP3A inhibitors (or inducer)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Peking University Cancer Hospital | Beijing | China |
Sponsors and Collaborators
- Zhejiang DTRM Biopharma
Investigators
- Study Director: Wei He, Ph.D., Zhejiang DTRM Biopharma
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DTRM_DTRMWXHS-12_001