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B-cell LymphomaPhase 1NCT03060850

A Phase I Study of AC0010 in Patients With CLL/ SLL, MCL, DLBCL and Other NHL

A Phase 1 study testing AC0010MA in people with B-cell Lymphoma, run by Hangzhou ACEA Pharmaceutical Research Co., Ltd. at 2 sites 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 The sponsor has not verified this record for over two years, so it may be out of date.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

This is an open label, dose escalation, phase I study to determine the recommended Phase 2 dose (PR2D) by assessing the DLT, safety and efficacy of AC0010 in patients with B-cell lymphoma. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
B-cell Lymphoma
What is being tested?
AC0010MA
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
184 participants
Where
2 sitesChina
Study dates
17 Mar 2017to 14 Dec 2020
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

  • Aged between 18 years and 75 years (included), and patients is over 60 years cannot have more than 3 kinds of heart, lung, liver and kidney complications
  • Histological confirmed CLL/SLL, MCL, non-GCB DLBCL
  • Measurable disease (NHL: At least 1 measurable site of disease [>1.5 centimeter [cm] in the long axis regardless of short axis measurement or >1.0 cm in the short axis regardless of long axis measurement, and clearly measurable in 2 perpendicular dimensions])
  • In dose escalation phase, other NHL (FL、WM、MZL、BL) patients who are relapsed refractory disease after at least 1 line of previous systemic therapy could be enrolled
  • Could supply stored For Formalin Fixed and Paraffin-Embedded (FFPE) slides or block to the lab for testing or could accept biopsy in the screening.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 2
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  • Any of the following hematology values within 14 days prior to inclusion and prior to the first dose of study drug :
  • Absolute neutrophil count (ANC) >= 750 cells/µL(0.75 x 109/L) without growth factors within 7 days prior to the first dose of study drug
  • Spontaneous Platelets count > 50,000 cells/mm3, exclude transfusion dependent thrombocytopenia
  • Adequate heart, liver, lung and renal function:
  • Alkaline phosphatase (ALP) <5* ULN
  • Creatinine determined by serum creatinine levels <=1.5 * ULN or a calculated creatinine clearance of >= 50 mL/min
  • LVEF≥50% as determined by Ultrasonic Cardiogram (UCG)
  • Any prior treatment (chemotherapy, radiotherapy or ) must be completed over 30 days or 5 *half life from the screening; all toxicities related to prior anticancer therapies must be recovered to grade ≤ 1 (CTCAE v 4.03)
  • Patients without central nervous system involvement
  • Life expectancy of more than 6 months
  • Women of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-hCG) or urine pregnancy test negative at Screening
  • Women without pregnant or breastfeeding

Who cannot join

  • Past history of major surgery within 4 weeks before signing the Informed consent form (ICF)
  • Patents with Central nervous system (CNS) lymphoma
  • Patients with prolymphocytic leukemia, patients with Richter's syndrome or suspected with Richter's syndrome
  • Known with primary mediastinal lymphoma • Previous treated with tyrosine kinase inhibitors (TKIs) (including BTK inhibitor) or within 3 months received mono-antibody treatment prior to the first dose of study drug
  • Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the patient has been free of the disease for ≥ 3 years
  • Use of any standard or experimental anti-cancer drug therapy within 30 days prior to the first dose of study drug
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  • Autotransplantation within 6 months prior to the first dose of study drug
  • Known received allogeneic stem cell transplantation
  • History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug
  • Requires treatment with anticoagulation with warfarin or equivalent vitamin K antagonists
  • Condition that requires treatment with a strong cytochrome P450 3A4/5 (CYP3A4/5) inhibitor
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months prior to the first dose of study drug, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
  • ECG showed abnormal PR, QT and QRS interval (defined as: 12 lead electrocardiogram QT interval corrected Bazett (QTcB) > 430 ms (male) or 450 ms (female), PR> 240 ms, QRS> 110 ms), and electrocardiogram in rhythm, conduction and morphology appeared on the clinical significance of abnormal, such as complete left bundle branch block, myocardial infarction occurred within 6 months; risk factors cause QTc prolongation such as heart failure, arrhythmia, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or first-degree relatives had less than 40 years of history of sudden death or bradycardia (heart rate less than 50 beats per minute)
  • Known HIV, active Hepatitis C Virus (HCV; RNA polymerase chain reaction (PCR)-positive) or active Hepatitis B Virus infection (HBs Ag positive or DNA PCR-positive) or any uncontrolled active systemic infection requiring intravenous (IV) antibiotics
  • All toxicities related to prior anticancer therapies recovered to grade ≤ 1 (exclude any grade alopecia)
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2.5 times upper limit of normal (ULN) and total bilirubin >1.5xULN
  • Blood urea nitrogen (BUN) or Cr >1.5x upper limits of normal (ULN)
  • Uncontrolled pericardial effusion and pleural effusion
  • History of Parkinson's disease; cerebellar disorders or other motor related diseases; patients with a history of pancreatitis
  • Investigator judgment that patient is unsuitable to participate in study
  • Uncontrolled pleural and pericardial effusion.
  • Pregnant and lactating women.

Trial locations and contacts

2 sites in 1 country.

Wanhong Xu, PhD contact

+86 571 28909102

kayla.liu@aceabio.com.cn

China2 sites, 2 recruiting

  • Peking Union Medical College Hospital

    Beijing, Beijing Municipality, 100000

    Bei Hu, PhD

    Recruiting

  • The First Affiliated Hospital,Zhejiang University

    Hangzhou, Zhejiang, 310000

    Jie Jin, MD, +86 13505716779, jiej0503@163.com

    Recruiting

Other trials in China

About this study

Official title: A Phase I Study of AC0010 in Patients With Relapsed or Refractory CLL/SLL, MCL, DLBCL and Other Non-Hodgkin B-Cell Lymphoma

This is an open label, dose escalation, phase I study to determine the recommended Phase 2 dose (PR2D) by assessing the DLT, safety and efficacy of AC0010 in patients with B-cell lymphoma.

Read the detailed description

This is an open label, dose escalation, phase I study to determine the PR2D by assessing the DLT, safety and efficacy of AC0010 in patients with B-cell lymphoma. This study includes two parts. During Part 1 Dose Escalation, the "3+3" design will be applied. Dose escalation will begin at dose level 1 = 400 mg. This dose escalation will be followed by an exploratory expansion phase in 3 or 4 groups of 15~41 patients each (CLL group, MCL group, non-germinal center B cell-like DLBCL group, and/or FL/WM(macroglobulinemia) group). The study will further evaluate the safety and efficacy of AC0010 in these patients in each group

Conditions
B-cell Lymphoma
Being tested
AC0010MA
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.

  • AC0010MADrug

    Also called AC0010

    Participants in the dose escalation cohorts will be treated with AC0010MA every 28 days

Study groups in NCT03060850
Study groupRoleWhat they receive
AC0010MAExperimentalThis is dose escalation study. Patients will receive AC0010MA 200mg bid,300mg bid,400mg bid or 500mg bid by mouth (the dose escalation whether ended depends on DLT and occupancy) everyday until intolerable toxicity or disease progression
Receives: Drug: AC0010MA

What is being measured

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

  1. Recommended phase II dose

    Determine the recommended phase II dose (RP2D) of AC0010 in patients with relapsed or refractory CLL/SLL, MCL, DLBCL and other Non-Hodgkin B-Cell lymphoma

    Measured: On cycle one, up to 28 days

Secondary outcomes (11)

  1. 24 hours occupancy of AC0010

    AC0010 occupancy of the Bruton's tyrosine kinase (BTK) active site up to 24 hours

    Measured: 24 hours

  2. Tolerability as measured by adverse events using CTCAE and clinical laboratory parameters

    Evaluation of tolerability of AC0010 measured by number, nature and severity of Adverse Events using CTCAE Version 4.03

    Measured: Approximately 36 months

  3. Tolerability as measured by number of subjects with dose limiting toxicities

    Evaluation of tolerability of AC0010 measured by number of subjects with dose limiting toxicities (DLTs)treatment

    Measured: on cycle one, up to 28 days

  4. Maximum tolerated dose (MTD)

    Maximum Tolerated Dose (MTD) as measured by the number of dose-limiting toxicities in each dose level

    Measured: on cycle one, up to 28 days

  5. Occupancy of AC0010 after continued treatment

    AC0010 occupancy of the BTK active site after continued treatment

    Measured: On first 4 cycles，up to 4 months

  6. Objective Response Rate (ORR)

    Safety and efficacy data will take place at the analysis time point

    Measured: Approximately 36 months

  7. Cmax

    Determine peak plasma concentration (Cmax) after oral administration of AC0010

    Measured: Day 1, Day 28, D112

  8. Tmax

    Time to reach maximum observed plasma concentration

    Measured: 5 min before-dose and 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1, 5 min before-dose and 2, 4, 8, 12 hours post-dose on Day 28, 5 min before-dose on Day 112

  9. t1/2

    plasma decay half-life

    Measured: 5 min before-dose and 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1, 5 min before-dose and 2, 4, 8, 12 hours post-dose on Day 28, 5 min before-dose on Day 112

  10. AUC(0-t)

    Area under the curve from time zero to the last quantifiable concentration

    Measured: 5 min before-dose and 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1, 5 min before-dose and 2, 4, 8, 12 hours post-dose on Day 28, 5 min before-dose on Day 112

  11. AUC(0-∞)

    Area under the curve from time zero to extrapolated infinity

    Measured: 5 min before-dose and 2, 3, 4, 6, 8, 12, 24 hours post-dose on Day 1, 5 min before-dose and 2, 4, 8, 12 hours post-dose on Day 28, 5 min before-dose on Day 112

Timeline

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

  1. First posted23 Feb 2017
  2. Study start17 Mar 2017
  3. Primary completion14 Dec 2019 (estimated)
  4. Study completion14 Dec 2020 (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
184 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03060850
Sponsor's protocol ID
AC201602AVTN05
Status last verified
Jan 2019
First submitted
10 Feb 2017
Last updated
1 Feb 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 AC0010MA in people with B-cell Lymphoma, run by Hangzhou ACEA Pharmaceutical Research Co., Ltd. at 2 sites 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 18 inclusion and 22 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 1 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 Wanhong Xu, PhD (+86 571 28909102, kayla.liu@aceabio.com.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended phase II dose (time frame: On cycle one, up to 28 days). 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 NCT03060850.

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 1 Feb 2019.

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