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Lymphoma, B-CellPhase 1NCT04173455

Study of the Safety, Tolerability and Pharmacokinetics of HZ-A-018 in Patients With B Cell Lymphoma

A Phase 1 study testing HZ-A-018 in people with Lymphoma, B-Cell, run by First Affiliated Hospital of Zhejiang University at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study is to establish the safety, tolerability, pharmacokinetics and RP2D (Recommended Phase II Dose) of orally administered HZ-A-018 in patients with B cell lymphoma who have at least failed or relapsed after first-line treatment. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Lymphoma, B-Cell
What is being tested?
HZ-A-018
Could I receive a placebo?
No, everyone receives an active treatment
How many people
46 participants
Where
1 siteChina
Study dates
28 Oct 2019to Feb 2022
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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).
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

1 site in 1 country.

Jianzhong Shentu, MD contact

+86057187236560

stjz@zju.edu.cn

China1 site, 1 recruiting

  • First Affiliated Hospital of Zhejiang University

    Hangzhou, Zhejiang, 310003

    Jianzhong Shentu, MD, +86057187236537, stjz@zju.edu.cn

    Wenbin Qian, MD

    Recruiting

Other trials in China

About this study

Official title: 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

The purpose of this study is to establish the safety, tolerability, pharmacokinetics and RP2D (Recommended Phase II Dose) of orally administered HZ-A-018 in patients with B cell lymphoma who have at least failed or relapsed after first-line treatment.

Being tested
HZ-A-018
Medical subject headings
Lymphoma, B-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • HZ-A-018Drug

    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.

Study groups in NCT04173455
Study groupRoleWhat they receive
HZ-A-018ExperimentalIn 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.
Receives: Drug: HZ-A-018

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Dose limiting toxicity assessment for each patient

    The "3+3" design will be applied in the dose-escalation part.

    Measured: At the end of the first 28 day cycle

  2. Maximum tolerated dose (MTD)

    The "3+3" design will be applied in the dose-escalation part.

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  3. Adverse events (AEs)

    Adverse events at each visit with the NCI CTCAE v5.0 used as a guide for the grading of severity.

    Measured: Up to 2 years

Secondary outcomes (8)

  1. Maximum plasma concentration (Cmax)

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  2. Time to reach maximum plasma concentration (Tmax)

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  3. Area under the plasma concentration-time curve from time zero to t (AUC0~t)

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  4. Area under the plasma concentration-time curve from time zero to infinity (AUC0~∞)

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  5. Elimination half-life (t1/2)

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  6. BTK (Brutons tyrosine kinase) occupancy in PBMCs(peripheral blood mononuclear cells)

    Measured: At the end of Cycle 1 (each cycle is 28 days)

  7. Objective response rate (ORR)

    The proportion of CR (complete response) and PR (partial response).

    Measured: Up to 2 years

  8. Duration of response (DOR)

    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.

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Nov 2019
  2. Study start28 Oct 2019
  3. Primary completionSep 2021 (estimated)
  4. Study completionFeb 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
46 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04173455
Sponsor's protocol ID
HZ-A-018-001
Status last verified
Nov 2019
First submitted
14 Nov 2019
Last updated
22 Nov 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing HZ-A-018 in people with Lymphoma, B-Cell, run by First Affiliated Hospital of Zhejiang University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 22 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Jianzhong Shentu, MD (+86057187236560, stjz@zju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicity assessment for each patient (time frame: At the end of the first 28 day cycle). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04173455.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2019.

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