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

NCT02891590 | Completed Phase 1

• 1 other identifier: DTRM_DTRMWXHS-12_001
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Lymphocytic Leukemia; B-cell Lymphomas

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events

  Confirm the safety and tolerability of multiple dose oral administration of DTRMWXHS-12 capsule

  Starting from date of first dose up to 30 days after last dose

Secondary Outcomes (1)

• Plasma concentrations of DTRMWXHS-12

  Days 1-28 (first treatment cycle)

Study Arms (1)

DTRMWXHS-12

EXPERIMENTAL

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

Interventions

DTRMWXHS-12 DRUG

DTRMWXHS-12

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Zhejiang DTRM Biopharma: lead

Study Sites (1)

Peking University Cancer Hospital

Beijing, China

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell

Interventions

DTRMWXHS-12

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, Non-Hodgkin; Lymphoma

Study Officials

• Wei He, Ph.D.

  Zhejiang DTRM Biopharma

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2016
• First Posted: September 7, 2016
• Study Start: September 1, 2016
• Primary Completion: February 1, 2019
• Study Completion: February 1, 2019
• Last Updated: April 14, 2020

Record last verified: 2020-04

Locations

CN (1)