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

Z

Zhejiang DTRM Biopharma

Status and phase

Completed
Phase 1

Conditions

Chronic Lymphocytic Leukemia
B-cell Lymphomas

Treatments

Drug: DTRMWXHS-12

Study type

Interventional

Funder types

Industry

Identifiers

NCT02891590
DTRM_DTRMWXHS-12_001

Details and patient eligibility

About

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.

Enrollment

13 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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)

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

13 participants in 1 patient group

DTRMWXHS-12
Experimental group
Description:
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.
Treatment:
Drug: DTRMWXHS-12

Trial contacts and locations

0

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Data sourced from clinicaltrials.gov

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