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

NCT03060850 | Unknown Phase 1

• 1 other identifier: AC201602AVTN05
• Study Type: interventional
• Target: 184
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

B-cell Lymphoma

Outcome Measures

Primary Outcomes (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

  On cycle one, up to 28 days

Secondary Outcomes (11)

• 24 hours occupancy of AC0010

  24 hours

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

  Approximately 36 months

• Tolerability as measured by number of subjects with dose limiting toxicities

  on cycle one, up to 28 days

• Maximum tolerated dose (MTD)

  on cycle one, up to 28 days

• Occupancy of AC0010 after continued treatment

  On first 4 cycles，up to 4 months

Study Arms (1)

AC0010MA

EXPERIMENTAL

This 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

Drug: AC0010MA

Interventions

AC0010MA DRUG

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

Also known as: AC0010

AC0010MA

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• Hangzhou ACEA Pharmaceutical Research Co., Ltd.: lead

Study Sites (2)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100000, China

RECRUITING

The First Affiliated Hospital,Zhejiang University

Hangzhou, Zhejiang, 310000, China

RECRUITING

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

abivertinib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jie Jin, MD

  The First Affiliated Hospital, Zhejiang University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wanhong Xu, PhD

CONTACT

+86 571 28909102; kayla.liu@aceabio.com.cn

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: February 10, 2017
• First Posted: February 23, 2017
• Study Start: March 17, 2017
• Primary Completion: December 14, 2019
• Study Completion: December 14, 2020
• Last Updated: February 1, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)