Clinical trial NCT04014205: A Study of Tyrosine Kinase Inhibitor Orelabrutinib (ICP-022) in Patients With r/r B-Cell Malignancies
Official title: A Phase I/II，Multicenter, Open-Label, Study of a Novel Bruton's Tyrosine Kinase Inhibitor, Orelabrutinib, in Patients With B-Cell Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Part 1：r/r B-cell Malignancies
Part 2：B-cell Malignancies
Lead sponsor: Beijing InnoCare Pharma Tech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2019-07-10
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: This is a Phase I/II, multicenter, open-label study to evaluate the safety, efficacy, tolerability, and pharmacokinetics of a novel BTK inhibitor, Orelabrutinib (ICP-022) in Patients with B-cell malignancies. The study contains two parts, Part 1 (dose escalation) and Part 2 (dose expansion).


Eligibility criteria: Inclusion Criteria:

1. Signed Informed Consent.
2. Age ≥ 18 years.
3. Part 1: Patients with histologically confirmed relapsed or refractory B-cell malignancies, including Grades 1-3a FL, MZL, MCL, and CLL/SLL.

   Part 2: Patients with histologically confirmed B-cell malignancies including r/r FL, r/r MZL and CLL/SLL with/without prior treatment.
4. Life expectancy (in the opinion of the investigator) of ≥ 4 months.
5. ECOG performance status of 0 \~1.
6. Must have adequate organ function.
7. Negative test results for HBV (\[HBsAg (-)\] and non-active HBV or HCV infection

Exclusion Criteria:

1. Pregnant or breast-feeding or intending to become pregnant during the study.
2. Prior treatment with systemic immunotherapeutic agents.
3. Known allergies to Orelabrutinib (ICP-022) or its excipients or infection with HIV.
4. Treatment with any chemotherapeutic agent, or any other investigational therapies within 4 weeks prior to first dose of the study drug.
5. History of allogeneic stem-cell (or other organ) transplantation or confirmed progressive PML.
6. Any external beam radiation therapy within 6 weeks prior to the first dose of the study drug.
7. Concurrent use of warfarin or other vitamin K antagonists or anticoagulation therapies or strong CYP3A inhibitor.
8. Active uncontrolled infections.
9. Recent infection requiring IV anti-infective treatment that was completed ≤ 14 days before the first dose of study drug.
10. Unresolved toxicities from prior anti-cancer therapy.
11. Medically apparent CNS lymphoma or leptomeningeal disease.
12. Current or previous history of CNS disease.
13. Major surgery or significant traumatic injury \< 28 days prior to the first dose of the study drug.
14. Patients with another invasive malignancy in the last 2 years.
15. Significant cardiovascular disease or active pulmonary disease.
16. Received systemic immunosuppressive medications.

Primary outcomes:
measure: Part 1 Dose Escalation：The maximum tolerated dose (MTD)
timeFrame: Incidence of dose limiting toxicities (DLTs) up to 28 days
measure: Part 2 Dose Expansion：ORR
timeFrame: Up to 2 years
Secondary outcomes:
measure: Part 1 Dose Escalation：Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability]
timeFrame: Up to 2 years
measure: Part 1 Dose Escalation：ORR
timeFrame: Up to 2 years
measure: Part 1 Dose Escalation：T1/2
timeFrame: Up to 2 years
measure: Part 2 Dose Expansion：Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability]
timeFrame: Up to 2 years
measure: Part 2 Dose Expansion：DOR
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic-Mayo Clinic Hospital-Phoenix
state: Arizona
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center
state: California
city: Los Angeles
country: United States
facility: Los Angeles Cancer Network - Good Samaritan Hospital Location
state: California
city: Rancho Mirage
country: United States
facility: Desert Hematology Oncology Medical Group, Inc.
state: California
city: Whittier
country: United States
facility: The Oncology Institute of Hope & Innovation
state: California
city: Fort Myers
country: United States
facility: Florida Cancer Specialists (FCS) South
state: Florida
city: Weeki Wachee
country: United States
facility: Asclepes Research Centers - Weeki Wachee
state: Florida
city: Elk Grove Village
country: United States
facility: Northwest Neurology - Rolling Meadows Office
state: Illinois
city: Skokie
country: United States
facility: Orchard Healthcare Research Inc.
state: Illinois
city: Goshen
country: United States
facility: Goshen Center for Cancer Care
state: Indiana
city: Topeka
country: United States
facility: Cotton O'Neil Cancer Center (Stormont-Vail Cancer Center)
state: Kansas
city: New Orleans
country: United States
facility: Tulane University School of Medicine - Tulane Cancer Center Comprehensive Clinic TCCCC
state: Louisiana
city: Annapolis
country: United States
facility: Anne Arundel Medical Center (AAMC) Oncology and Hematology
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic - Minnesota
state: Minnesota
city: Saint Cloud
country: United States
facility: Coborn Cancer Center
state: Minnesota
city: Lincoln
country: United States
facility: Southeast Nebraska Cancer Center
state: Nebraska
city: Florham Park
country: United States
facility: Summit Medical Group
state: New Jersey
city: Westbury
country: United States
facility: Clinical Research Alliance
state: New York
city: Canton
country: United States
facility: Gabrail Cancer Research Center
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh - Hillman Cancer Center
state: Pennsylvania
city: Sayre
country: United States
facility: Guthrie Cancer Center
state: Pennsylvania
city: Watertown
country: United States
facility: Prairie Lakes Cancer Center
state: South Dakota
city: Chattanooga
country: United States
facility: Tennessee Oncology - Chattanooga Oncology & Hematology Associates
state: Tennessee
city: Knoxville
country: United States
facility: Tennessee Cancer Specialists
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute - Tennessee Oncology
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Spokane
country: United States
facility: Medical Oncology Associates PS (dba Summit Cancer Centers)
state: Washington
city: Be'er Sheva
country: Israel
facility: Soroka Medical Center
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Cherkasy
country: Ukraine
facility: Cherkassy Regional Oncology Center
city: Khmelnytskyi
country: Ukraine
facility: Khmelnytskyi Regional Hospital
city: Kropyvnytskyi
country: Ukraine
facility: St. Luke's Hospital - Medical and Diagnostic Center
city: Kyiv
country: Ukraine
facility: National Cancer Institute
city: Lviv
country: Ukraine
facility: Institute of Blood Pathology and Transfusion Medicine
city: Uzhgorod
country: Ukraine
facility: Transcarpathian Regional Clinical Hospital named after Andrii Novak
Study officials:
References: