- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04173455
Study of the Safety, Tolerability and Pharmacokinetics of HZ-A-018 in Patients With B Cell Lymphoma
Phase I Study to Evaluate the Safety, Tolerability and Pharmacokinetic Characteristics of Bruton Tyrosine Kinase (BTK) Inhibitor HZ-A-018 in Patients With B-Cell Lymphoma
Study Overview
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Jianzhong Shentu, MD
- Phone Number: +86057187236560
- Email: stjz@zju.edu.cn
Study Locations
-
-
Zhejiang
-
Hangzhou, Zhejiang, China, 310003
- Recruiting
- First Affiliated Hospital of Zhejiang University
-
Contact:
- Jianzhong Shentu, MD
- Phone Number: +86057187236537
- Email: stjz@zju.edu.cn
-
Principal Investigator:
- Wenbin Qian, MD
-
Principal Investigator:
- Jianzhong Shentu, MD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Women and men between 18 and 75 years old, voluntarily signed a informed consent.
- Body weight ≥ 45 kg.
- ECOG (Eastern Cooperative Oncology Group) performance status of 0~1.
- Life expectancy (in the opinion of the investigator) of ≥ 4 months.
- Patients with histologically or cytologically confirmed mature B-cell lymphoma according to 2017 WHO (World Health Organization) classification, including chronic lymphocytic leukemia/ small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), Waldenström's Macroglobulinemia (WM) and diffuse large B-cell lymphoma (DLBCL); previous treatment for DLBCL patients must include Rituxan (CD20 monoclonal antibody) and anthracyclines-based therapy and meet one of the following criteria: 1)complete response was not achieved after previous second line therapy; 2) disease progression occurred during any of previous treatment; 3) the duration of stable disease was ≤ 6 months; 4) Disease progression or recurrence occurred within 12 months after autologous hematopoietic stem cell transplantation; CLL and other indolent B-cell NHL patients must meet one of the following criteria: at least failure to respond to first line therapy (SD or PD after treatment with Rituxan-based and alkylating agents or anthracyclines therapy), any response (CR or PR) and progression after stable disease.
- Measurable disease for SLL, MCL, FL, DLBCL and MZL: lymph node lesions>1.5 cm diameter in at least one dimension or any of external node lesions >1.0 cm diameter in at least one dimension; for CLL, peripheral blood monoclonal lymphocytes ≥ 5.0×109/L; for WM, IgM﹥2×ULN (upper limit of normal).
- Any non-hematologic toxicity associated with prior treatment should recover to grade ≤ 1 (according to NCI CTCAE version 5.0).
- Adequate hematological function (no blood transfusion, no use of G-CSF (G-Colony stimulating factor) and no drug correction within 14 days of screening): absolute neutrophil count (ANC) ≥ 0.75 × 109 /L (≥ 0.5×109/L if presence of bone marrow infiltration); platelet count ≥ 50 × 109/L; Hgb ≥ 8.0 g/dL (≥7.0 g/dL if presence of bone marrow infiltration for WM and CLL).
- Adequate renal function: serum creatinine ≤ 1.5 × ULN or estimated creatinine clearance ≥ 60 mL/min (Male: Cr (mL/min) = (140- age) × weight (kg) /72× serum creatinine concentration (mg/dl); Female: Cr (ml/min) = (140- age) × weight (kg) /85× serum creatinine concentration (mg/dl)).
- Adequate liver function: total serum bilirubin ≤ 1.5 x ULN (≤3.0×ULN if presence of liver metastasis); AST and ALT ≤ 2.5 x ULN (≤5.0×ULN if presence of liver metastasis).
- Female of childbearing age and males subjects with fertility must practice at least one of the following effective contraception methods throughout the study and within 90 days of discontinuing study drug: total abstinence from sexual intercourse, physical contraception, or hormonal contraceptive initiated at least 3 months prior to first dose of study drug.
- Male subjects must not donate sperm from initial study drug administration, until 90 days after drug discontinuation.
- Ability to swallow oral capsules without difficulty.
- Willing to follow visit schedules, drug administration schedules, laboratory tests and other test procedures.
Exclusion Criteria:
- Prior BTK inhibitor treatment.
- Infiltration of CNS (central nervous system) by lymphoma.
- Prior organ transplantation or allogeneic hematopoietic stem cell transplantation.
- History of other active malignancies, with exception of basal cell carcinoma of skin, squamous cell carcinoma of skin, cervical carcinoma in situ, or other carcinoma in situ with curative therapy and no recurrence within 5 years.
- Uncontrolled systemic infection or infection requiring intravenously anti-microbial therapy.
- Major surgery or severe trauma within 4 weeks before signing the informed consent.
- Any of the following conditions occurred within the past 6 months: significant cardiac diseases, such as congestive heart failure (NYHA III or IV heart failure), myocardial infarction, and unstable angina pectoris; significant ECG abnormalities, such as atrial fibrillation of any grade, grade II atrioventricular block or grade III atrioventricular block or QTc (F) > 470 msec (female) or > 450 msec (male); other arrhythmias that require treatment.
- Active renal, neurological/psychiatric, liver or endocrine disease, in the opinion of the investigator, would adversely impact on his/her participating in the study.
- Inability to comply with study procedures.
- Stroke or cerebral hemorrhage occurred within 6 months prior to the first dose of the study drug.
- Uncontrolled hypertension, in the opinion of the investigator.
- Previous or active pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radioactive pneumonia, etc.
- Active hepatitis B or C infection (HBV: HBV-DNA ≥1000 IU/mL; hcv: HCV RNA positive with abnormal liver function) or human immunodeficiency virus (HIV) infection or syphilis.
- Active enteritidis , chronic diarrhea, known diverticulosis, or prior gastrectomy or gastric banding, or other conditions that affect absorption.
- Concurrent use of a strong CYP3A4/5 inhibitor (ketoconazole, itraconazole, voriconazole, posaconazole, talimycin, and clarithromycin) or inducers (carbamazepine, rifampicin, phenytoin sodium, etc.) during the study.
- Concurrent use of warfarin or vitamin K antagonists or anticoagulation therapies, or having bleeding tendency or coagulation disorder, within 4 weeks prior to signing the informed consent or during the study.
- Treatment with anti-tumor therapy (including chemotherapy, radiotherapy, immunotherapy, targeted therapy, traditional Chinese medicine or other clinical research therapy) within 4 weeks prior to signing the informed consent; anti-tumor treatment with steroid hormone (dose equivalent to prednisone > 20 mg) within 7 days prior to signing the informed consent.
- Pregnant, breast-feeding or intending to have children with their partners during the study and within 3 months after discontinuation of the study.
- Participating in another clinical trial and taking the drug within 4 weeks prior to signing the informed consent.
- In the opinion of the investigator, other factors that may cause subjects to be forced to terminate the study, such as other serious diseases, serious laboratory abnormalities, and other factors that may affect subjects' safety or test data and blood sample collection.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: HZ-A-018
In the dose-escalation part, the "3+3" design will be applied. If the subject does not have a DLT during the first 28-day cycle, those who with stable or remission of disease may continue to receive treatment until disease progression, intolerable toxicity or the subject no longer benefits. In the dose-expansion part, HZ-A-018 will be administered for several 28-day cycles until disease progression, intolerable toxicity or the subject no longer benefits. |
In the dose-escalation part, subjects will be assigned to five cohorts with increaing dose level to determine DLT and MTD during the first 28-day cycle. In the expansion part, subjects will be assigned to two fixed dose corhort. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose limiting toxicity assessment for each patient
Time Frame: At the end of the first 28 day cycle
|
The "3+3" design will be applied in the dose-escalation part.
|
At the end of the first 28 day cycle
|
Maximum tolerated dose (MTD)
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
|
The "3+3" design will be applied in the dose-escalation part.
|
At the end of Cycle 1 (each cycle is 28 days)
|
Adverse events (AEs)
Time Frame: Up to 2 years
|
Adverse events at each visit with the NCI CTCAE v5.0 used as a guide for the grading of severity.
|
Up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Maximum plasma concentration (Cmax)
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
|
At the end of Cycle 1 (each cycle is 28 days)
|
|
Time to reach maximum plasma concentration (Tmax)
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
|
At the end of Cycle 1 (each cycle is 28 days)
|
|
Area under the plasma concentration-time curve from time zero to t (AUC0~t)
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
|
At the end of Cycle 1 (each cycle is 28 days)
|
|
Area under the plasma concentration-time curve from time zero to infinity (AUC0~∞)
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
|
At the end of Cycle 1 (each cycle is 28 days)
|
|
Elimination half-life (t1/2)
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
|
At the end of Cycle 1 (each cycle is 28 days)
|
|
BTK (Brutons tyrosine kinase) occupancy in PBMCs(peripheral blood mononuclear cells)
Time Frame: At the end of Cycle 1 (each cycle is 28 days)
|
At the end of Cycle 1 (each cycle is 28 days)
|
|
Objective response rate (ORR)
Time Frame: Up to 2 years
|
The proportion of CR (complete response) and PR (partial response).
|
Up to 2 years
|
Duration of response (DOR)
Time Frame: Up to 2 years
|
Duration of response is defined as the time from the date of first occurrence of CR (complete response) or PR (partial response) to the date of the first documented PD (progressive disease) or death due to any cause.
|
Up to 2 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jianzhong Shentu, First Affiliated Hospital of Zhejiang University
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- HZ-A-018-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Lymphoma, B-Cell
-
Iksuda Therapeutics Ltd.RecruitingFollicular Lymphoma | B-cell Lymphoma | Mantle Cell Lymphoma | Diffuse Large B Cell Lymphoma | B-cell Non-Hodgkin LymphomaAustralia, Canada, United States
-
Nathan DenlingerBristol-Myers SquibbRecruitingB-Cell Non-Hodgkin Lymphoma-Recurrent | Diffuse Large B-Cell Lymphoma-Recurrent | Follicular Lymphoma-Recurrent | High Grade B-Cell Lymphoma-Recurrent | Primary Mediastinal Large B-Cell Lymphoma-Recurrent | Transformed Indolent B-Cell Non-Hodgkin Lymphoma to Diffuse Large B-Cell Lymphoma-Recurrent and other conditionsUnited States
-
AstraZenecaRecruitingFollicular Lymphoma | Diffuse Large B Cell Lymphoma | High-grade B-cell Lymphoma | B-cell Non Hodgkin LymphomaKorea, Republic of, United States, Japan, Australia, Taiwan
-
Memorial Sloan Kettering Cancer CenterRecruitingLymphoma | Lymphoma, B-Cell | DLBCL - Diffuse Large B Cell Lymphoma | Large B-cell Lymphoma | Large-cell Lymphoma | Mediastinal B-Cell Diffuse Large Cell LymphomaUnited States
-
Massachusetts General HospitalVarian Medical SystemsRecruitingLymphoma, B-Cell | Follicular Lymphoma | Mantle Cell Lymphoma | Diffuse Large B Cell Lymphoma | Refractory Lymphoma | High-grade B-cell Lymphoma | Relapsed Cancer | Mediastinal Large B-cell LymphomaUnited States
-
University of ChicagoMerck Sharp & Dohme LLCRecruitingLymphoma | Lymphoma, B-Cell | B Cell Lymphoma | Diffuse Large B Cell Lymphoma | High-grade B-cell LymphomaUnited States
-
Qian WenbinNot yet recruitingDiffuse Large B Cell Lymphoma | Refractory Diffuse Large B-Cell Lymphoma | Relapsed Diffuse Large B-Cell LymphomaChina
-
Curocell Inc.RecruitingHigh-grade B-cell Lymphoma | Diffuse Large B-cell Lymphoma (DLBCL) | Primary Mediastinal Large B-Cell Lymphoma (PMBCL) | Transformed Follicular Lymphoma (TFL) | Refractory Large B-cell Lymphoma | Relapsed Large B-cell LymphomaKorea, Republic of
-
University of NebraskaBristol-Myers SquibbRecruitingFollicular Lymphoma | Refractory Non-Hodgkin Lymphoma | High-grade B-cell Lymphoma | DLBCL - Diffuse Large B Cell Lymphoma | Relapsed Non-Hodgkin Lymphoma | Mediastinal Large B-cell Lymphoma | Indolent B-Cell Non-Hodgkin LymphomaUnited States
-
Northwestern UniversityNational Cancer Institute (NCI)Active, not recruitingDiffuse Large B-Cell Lymphoma | Diffuse Large B-Cell Lymphoma, Not Otherwise Specified | High Grade B-Cell Lymphoma, Not Otherwise Specified | T-Cell/Histiocyte-Rich Large B-Cell Lymphoma | High Grade B-Cell Lymphoma With MYC and BCL2 and/or BCL6 Rearrangements | Diffuse Large B-Cell Lymphoma... and other conditionsUnited States
Clinical Trials on HZ-A-018
-
Johns Hopkins UniversityNational Institute on Aging (NIA)Active, not recruiting
-
NS Pharma, Inc.CompletedPrimary Myelofibrosis | Post-Polycythemia Vera Myelofibrosis | Post-Essential Thrombocythemia MyelofibrosisUnited States
-
TakedaTakeda Development Center Americas, Inc.TerminatedCrohn DiseaseUnited States, Germany, Austria, France, United Kingdom
-
Medibiofarma S.L.Recruiting
-
MedtronicNeuroCompleted
-
Antengene Discovery LimitedRecruitingAdvanced Solid Tumors | Hematological MalignanciesAustralia
-
Hangzhou Highlightll Pharmaceutical Co., LtdCompleted
-
NS Pharma, Inc.Nippon Shinyaku Co., Ltd.RecruitingPrimary Myelofibrosis | Post-polycythemia Vera Myelofibrosis | Post-essential Thrombocythemia MyelofibrosisUnited States, Korea, Republic of, Malaysia, Italy, Germany, Poland, United Kingdom, Thailand, Turkey
-
Seton Healthcare FamilyAbbott Medical Devices; University of Texas at AustinTerminated