Clinical Trials /

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

NCT04014205

Description:

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).

Related Conditions:
  • Chronic Lymphocytic Leukemia
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma
  • Small Lymphocytic Lymphoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: ICP-CL-00107
  • NCT ID: NCT04014205

Conditions

  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Follicular Lymphoma
  • Mantle Cell Lymphoma
  • Marginal Zone Lymphoma

Interventions

DrugSynonymsArms
ICP-022ICP-022 (Higher Dose)

Purpose

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).

Trial Arms

NameTypeDescriptionInterventions
ICP-022 (Lower Dose)Experimental100 mg, Once a day (QD)
  • ICP-022
ICP-022 (Higher Dose)Experimental150 mg, QD
  • ICP-022

Eligibility 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The maximum tolerated dose (MTD)
Time Frame:Incidence of dose limiting toxicities (DLTs) up to 28 days
Safety Issue:
Description:

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Beijing InnoCare Pharma Tech Co., Ltd.

Last Updated

October 9, 2019