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A Study of Tyrosine Kinase Inhibitor ICP-022 in Patients With r/r B-Cell Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04014205
Recruitment Status : Recruiting
First Posted : July 10, 2019
Last Update Posted : May 27, 2020
Sponsor:
Information provided by (Responsible Party):
Beijing InnoCare Pharma Tech Co., Ltd.

Brief Summary:
This is a Phase I, multicenter, open-label, dose-escalation study to evaluate the safety, tolerability and pharmacokinetics of a novel BTK inhibitor, ICP-022. During this study, dose escalation will be conducted in patients diagnosed with refractory/relapsed (r/r) B-cell malignancies including only patients with Grades1-3a follicular lymphoma (FL); marginal zone lymphoma (MZL); mantle cell lymphoma (MCL); and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Follicular Lymphoma Mantle Cell Lymphoma Marginal Zone Lymphoma Drug: ICP-022 Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I, Multicenter, Open-Label, Dose Escalation Study of a Novel Bruton's Tyrosine Kinase Inhibitor, ICP-022, in Patients With Relapsed/Refractory B-Cell Malignancies
Actual Study Start Date : November 18, 2019
Estimated Primary Completion Date : August 17, 2020
Estimated Study Completion Date : July 3, 2023


Arm Intervention/treatment
Experimental: ICP-022 (Lower Dose)
100 mg, Once a day (QD)
Drug: ICP-022
ICP-002 The drug product is a white, round, uncoated tablet

Experimental: ICP-022 (Higher Dose)
150 mg, QD
Drug: ICP-022
ICP-002 The drug product is a white, round, uncoated tablet




Primary Outcome Measures :
  1. The maximum tolerated dose (MTD) [ Time Frame: Incidence of dose limiting toxicities (DLTs) up to 28 days ]

Secondary Outcome Measures :
  1. Incidence and severity of treatment-emergent adverse events (AEs) [Safety and Tolerability] [ Time Frame: Up to 2 years ]
    The incidence and severity of treatment-emergent AEs will be collected and the safety and tolerability of ICP-022 will be assessed


Other Outcome Measures:
  1. Objective response rate (ORR) [ Time Frame: Up to 2 years ]
    ORR of ICP-022 will be assessed by the investigator using standard criteria for Non-Hodgkin's lymphoma [2014 Lugano Classification criteria International working group non-hodgkin's lymphoma (IWGNHL) (Cheson et al., 2014) and the International Workshop on Chronic Lymphocytic Leukemia (IWCLL), (Hallek et al., 2008)]

  2. Elimination half-life (T1/2) [ Time Frame: 28 days/cycle, Cycle1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle2 Day1 pre-dose (-10 minutes) ]
  3. Total plasma exposure - Area under the concentration time curve (AUC) [ Time Frame: 28 days/cycle, Cycle1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle Day1 pre-dose (-10 minutes) ]
  4. Time to reach maximum observed plasma concentration (Tmax) [ Time Frame: 28 days/cycle, Cycle1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle2 Day1 pre-dose (-10 minutes) ]
  5. Maximum plasma concentration observed (Cmax) [ Time Frame: 28 days/cycle, Cycle 1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle 2 Day1 pre-dose (-10 minutes) ]
  6. Minimum plasma concentration (Cmin) under steady-state conditions within a dosing interval [ Time Frame: 28 days/cycle, Cycle1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle2 Day1 pre-dose (-10 minutes) ]
  7. clearance (CL) [ Time Frame: 28 days/cycle, Cycle1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle2 Day1 pre-dose (-10 minutes) ]
  8. Volume of distribution at steady-state (Vss) [ Time Frame: 28 days/cycle, Cycle 1 Day 1 and Day 8 pre-dose (-10 minutes), 15 minutes, 30 minutes, 1, 2, 4, 8 and 24 hours (before dosing on next day) after study medication administration; Cycle2 Day1 pre-dose (-10 minutes) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed Informed Consent
  2. All subjects must meet criteria for requiring therapy at time of enrollment (see treatment indications below)
  3. Age ≥ 18 years
  4. Patients with histologically confirmed relapsed or refractory B-cell malignancies, including only patients with Grades 1-3a FL, MZL, MCL, and CLL/SLL
  5. Patient must had received ≥1 or ≤ 4 prior therapies with documented failure to achieve at least partial response, or disease progression after the most recent systemic treatment
  6. Patient must have ≥1 measurable lesion site on CT scan (>1.5 cm in longest dimension). Lesions in anatomical locations (such as extremities or soft tissue lesions) that are not well visualized by CT may be measured by MRI instead (Subjects with spleen-only disease are considered as not having measurable disease)
  7. Electrocorticogram(ECOG) performance status of 0 ~1
  8. Life expectancy (in the opinion of the investigator) of ≥ 4 months
  9. Adequate liver function at time of screening: Total bilirubin ≤ 2.0 x Upper Limit of Normal (ULN) (Patients with documented history of Gilbert's Syndrome and in whom total bilirubin elevations are accompanied by elevated indirect bilirubin are eligible); Aspartate aminotransferase(AST)/ Alanine Aminotransferase(ALT) ≤ 2.5 × ULN
  10. Coagulation test: at time of screening, international normalized ratio (INR) ≤1.5, and the activated partial thromboplastin time (APTT) ≤ 1.5× ULN
  11. Adequate hematological function at time of screening: complete blood count tests should be independent of support therapies (i.e., growth factors, or transfusion) and fulfill these criteria: neutrophil count ≥ 1.5 × 109 /L, platelet count ≥ 75 × 109/L, hemoglobin ≥ 80 g/L; if presence of bone marrow infiltration, neutrophil count ≥ 1.0 × 109 /L and platelet count ≥ 50× 109 /L
  12. Adequate renal function at time of screening: serum creatinine ≤ 1.5 × ULN or creatinine clearance by Cockcroft-Gault formula ≥ 60 mL/min
  13. Negative test results for Hepatitis B Virus(HBV) ([HBsAg (-)] and non-active HBV or Hepatitis C Virus(HCV) infection:

    • Patients who are positive for anti-Hepatitis B Virus core(anti-HBc) antibody must be negative for HBV DNA by Polymerase Chain Reaction (PCR) to be eligible for study participation
    • Patients who are positive for HCV antibody must be negative for HCV RNA by PCR to be eligible for study participation.
  14. Negative serum pregnancy test within 7 days prior to study treatment in women of childbearing potential. Women who are not of childbearing potential and who are considered to be postmenopausal (≥ 12 months of non-therapy amenorrhea) or surgically sterile (absence of ovaries and/or uterus) are not required to have a pregnancy test.
  15. Patients must agree to either remain completely abstinent or to use two effective contraceptive methods that result in a failure rate of <1 % per year from screening until (a) 1 month if the patient is a male or (b) 2 months if patient is a female after the last dose of Innocare Pharma-022(ICP-022).

Exclusion Criteria:

  1. Pregnant or breast-feeding or intending to become pregnant during the study
  2. Prior treatment with systemic immunotherapeutic agents, including but not limited to cytokine therapy and anti-CTLA4, anti-Programmed death 1(anti-PD1) and anti- Programmed cell death 1 ligand 1(anti-PDL1) therapeutic antibodies, within 12 weeks or five half-lives of the drug, whichever is shorter, before first dose of ICP-022
  3. Treatment with any Bruton's tyrosine kinase inhibitor(BTKi), phosphatidylinositol 3 kinase( PI3Ki) or B-cell lymphoma-2(BCL-2) inhibitor
  4. Patients with known allergies to ICP-022 or its excipients
  5. Treatment with any chemotherapeutic agent, or treatment with any other investigational therapies including but not limited to anti-cancer agent (defined as treatment for which there is currently no regulatory authority approved indication) within 4 weeks prior to first dose of ICP-022
  6. History of allogeneic stem-cell (or other organ) transplantation
  7. Any external beam radiation therapy within 6 weeks prior to the first dose of the study drug
  8. Concurrent use of warfarin or other vitamin K antagonists or anticoagulation therapies
  9. Concurrent use of a strong Cytochrome P450 3A (CYP3A) inhibitor. Subjects who have received a strong CYP3A inhibitor prior to entering the study must have discontinued therapy for at least 5 half-lives of the prohibited medication.
  10. Active uncontrolled infections
  11. Recent infection requiring IV anti-infective treatment that was completed ≤14 days before the first dose of study drug
  12. Known infection with HIV, seropositive status
  13. Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) ≤ Grade 1, or to the levels dictated in the eligibility criteria with the exception of alopecia.
  14. Patient with history of confirmed progressive multifocal leukoencephalopathy (PML)
  15. Medically apparent central nervous system(CNS) lymphoma or leptomeningeal disease
  16. Current or past history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease

    • Patients with a history of stroke who have not experienced a stroke or transient ischemic attack in the past 2 years and have no residual neurologic deficits as judged by the investigator, are allowed

  17. Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, abusing of alcohol or illegal drugs including non-prescribed marijuana within last 6 months from screening.
  18. Major surgery or significant traumatic injury < 28 days prior to the first dose of ICP-022 (excluding biopsies) or anticipation of the need for major surgery during study treatment
  19. Patients with another invasive malignancy in the last 2 years (with the exception of basal cell carcinoma and tumors deemed by the investigator to be of low likelihood for recurrence)
  20. Significant cardiovascular disease such as New York Heart Association (NYHA) Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina)
  21. Significant active pulmonary disease (e.g., bronchospasm and/or obstructive pulmonary disease)
  22. Administration of a live, attenuated vaccine within 28 days before Cycle 1, Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  23. Received systemic immunosuppressive medications (including but not limited to cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor agents) with the exception of corticosteroid treatment < 20 mg/day prednisone or equivalent within 7 days prior to first dose of ICP-022

    • Inhaled and topical steroids are permitted

  24. Unable to swallow tablets or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
  25. Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04014205


Contacts
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Contact: Rashidah Cornitcher +1 (919) 800-2628 ext +1 (215) 760-6 Rashidah.Cornitcher@syneoshealth.com

Locations
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United States, Louisiana
Tulane University School of Medicine - Tulane Cancer Center Comprehensive Clinic TCCCC Recruiting
New Orleans, Louisiana, United States, 70112
Contact: Saba Nakhle         
United States, Michigan
University of Michigan Health System Recruiting
Ann Arbor, Michigan, United States, 48103
Contact: Phillips J Phillips         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Yucai Wang         
United States, Montana
St Vincent Frontier Cancer Center Recruiting
Billings, Montana, United States, 59101
Contact: Cobb W Patrick         
United States, New Jersey
Summit Medical Group Recruiting
Florham Park, New Jersey, United States, 07932
Contact: Gallinson H David         
United States, New York
Clinical Research Alliance Recruiting
New Hyde Park, New York, United States, 11040
Contact: Coleman Morton         
United States, Texas
MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Michael (Luhua) Wang         
Contact    713-792-2860    miwang@mdanderson.org   
United States, Washington
Medical Oncology Associates PS (dba Summit Cancer Centers) Recruiting
Spokane, Washington, United States, 99201
Contact: Chaudhry Arvind         
Sponsors and Collaborators
Beijing InnoCare Pharma Tech Co., Ltd.
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Responsible Party: Beijing InnoCare Pharma Tech Co., Ltd.
ClinicalTrials.gov Identifier: NCT04014205    
Other Study ID Numbers: ICP-CL-00107
First Posted: July 10, 2019    Key Record Dates
Last Update Posted: May 27, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia
Leukemia, B-Cell
Lymphoma, B-Cell