Phase Ib Clinical Study of Keynatinib

Recruiting now · Phase 1

Conditions studied: Lymphoma, B-Cell

In brief

The purpose of this study is to evaluate the efficacy, safety, PK characteristics in subjects with relapsed/refractory B-cell lymphoma. Furthermore, the relationship between the exposure level of Keynatinib and its efficacy and safety, the penetration rate of keynatinib in the Blood-Brain Barrier (BBB) and its PK characteristics in cerebrospinal fluid in R/R-PCNSL patients, the relationship between the BTK receptor occupancy rate and the efficacy are also evaluated.

Key facts

Study ID

NCT04807881

Run by

Medolution Ltd.

People needed

75

Starts

2020-09-24

Expected to finish

2028-04-10

Last updated by the study team

2025-01-22

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Unlimited gender, age ≥ 18 years (including critical value)-Cohort 1/2/3;
• Voluntarily participate in the study and sign the ICF, follow the trial treatment protocol and interview plan-Cohort 1/2/3;
• The subject's disease diagnosis meets all of the following conditions:
• Cohort 1:
• Primary central nervous system lymphoma (PCNSL) confirmed by pathology;
• For relapsed or refractory PCNSL, at least first line treatment must be given to Central Nervous System (CNS) lesions;
• Brain Magnatic resonance Imaging (MRI) or Computerized tomography (CT) shows solid lesions of PD;
• Cohort 2:
• CLL/SLL diagnosed according to IWCLL 2008 standards;
• Refractory or relapsed CLL/SLL that previously received at least first-line systemic treatment. First-line treatment is defined as at least 2 cycles of standard protocol or clinical trial research protocol completed based on current guidelines;
• Accord with at least one indication of CLL / SLL that requiring treatment;
• There is medical record confirming that it is invalid or Progression Disease occurs after response for the latest treatment;
• CT /MRI shows measurable lesions, which is defined as at least one lymph node with a maximum axis of more than 1.5 cm and with 2 measurable vertical dimension;
• It is allowed to include the patients with a stable condition involving the central nervous system;
• Cohort 3:
• Mantle cell lymphoma diagnosed by histopathology: including that t (11; 14) (q13; q32) positive by cytogenetic test and / or cyclin D1 highly expressed by immunohistochemistry;
• Who have been pretreated with > 1 but failed in ≤ 3 different chemotherapies and / or targeted drugs treatment.
• There is a medical record confirming that it is invalid or Progression Disease occurs after response for the latest treatment;
• CT / MRI shows measurable lesions, which is defined as the longest diameter (of ≥1 lymph node) > 1.5 cm, and 2 vertical diameters is clearly measurable;
• It is allowed to include the patients with a stable condition involving the central nervous system;
• When screening, the status score of Eastern Cooperative Oncology Group (ECOG) is 0 to 2 points-Cohort 1/2/3;
• Estimated survival time ≥ 4 months-Cohort 1/2/3;
• Subjects have appropriate organ functions, the main organ functions meet the following criteria:
• Blood routine: Neutrophil absolute value ≥ 1.0(in cohort1, 0.75 in cohort 2/3)×109 /L, platelet ≥ 75(in cohort1, 50 in cohort 2/3, 30×109/L are acceptable if CLL patients have bone marrow involvement, transfusion-dependent thrombocytopenia is excluded )×109 /L, hemoglobin ≥ 80 g/L(in cohort1). [No blood transfusion and hematopoietic stimulating factor are used within 21 days (7 days in cohort 2/3) before the first administration-Chort1];
• Blood biochemistry: Total bilirubin (TBIL) ≤ 2 × ULN (unless diagnosed as Gilbert syndrome), Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 × ULN; serum creatinine ≤ 2 × ULN or creatinine clearance rate ≥ 50 ml / min (calculated according to Cockcroft Gault formula)-Cohort 1/2/3;

You may not qualify if…

• Cohort 1: R/R-PCNSL
• PCNSL is pathologically diagnosed as T-cell lymphoma;
• Have previously received any of the following treatments:
• Chemotherapy, targeted therapy, radiotherapy or antibody based anti-tumor therapy are used within 4 weeks before the first administration or within 5 half-lives (whichever is shorter);
• Have previously received the treatment of B Cell Receptor (BCR) inhibitors (such as BTK, phosphoinositide kinase 3 kinase [PI3K] or SYK inhibitors) or BCL-2 inhibitors (such as ABT-199) or Chimeric Antigen Receptor T-Cell Immunotherapy (CAR-T) or a bispecific antibody drug;
• Have received Allogenetic Haematopoietic Stem Cell Transplantation (Allo-HSCT) or other organ transplants (except for those who have received ASCT more than six months);
• Take ≥ 8 mg dexamethasone or equivalent daily to control lymphoma symptoms;
• CNS external beam radiotherapy within 21 days before the first administration;
• The systemic immunosuppressants, including cyclosporine A, tacrolimus, sirolimus and other drugs, haven't stopped 28 days before the first use of the study drug, or > 5 mg/day of prednisone or its equivalent has been taken for long period;
• Have other malignant tumors within 3 years, except for the curable basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of cervix or breast;
• Non-hematologic toxicity of the previous anti-tumor treatment has not recovered to ≤ grade 1 (except for hair loss);
• Have uncontrollable or severe cardiovascular disease, including:
• Congestive heart failure with New York Heart Association (NYHA) grade II or higher, unstable angina, myocardial infarction within 6 months before first study drug administration, or arrhythmia requiring treatment during screening, Left Ventricular Ejection Fraction (LVEF) <50% ;
• Primary cardiomyopathy (such as dilated cardiomyopathy, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, restrictive cardiomyopathy, and atypical cardiomyopathy);
• Clinically significant QTc interval prolonged medical history, or the QTc interval of screening period > 470 ms in female, and > 450 ms in male;
• Uncontrollable high blood pressure (on the basis of improving life style, with 2 or more antihypertensive drugs (including diuretics) that will be reasonably tolerable and sufficient for more than one month being applied, the blood pressure has not reached to the standard yet, or the blood pressure could only be effectively controlled by taking 4 or more antihypertensive drugs);
• Have active bleeding within 2 months before screening or are taking anticoagulant/antiplatelet drugs, or the investigators believe that there is a clear bleeding tendency (such as esophageal varices with bleeding risk, or a locally active ulcer lesions);
• Have medical history of deep vein thrombosis or pulmonary embolism;
• Have medical history of stroke or intracranial hemorrhage within 6 months before taking the study drug, except for intracranial hemorrhage due to surgical sequelae;
• Have clinically significant gastrointestinal abnormalities, which might affect drug intake, transport or absorption (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
• Have serious or active infection requiring systematic anti infection treatment;
• At screening, patients with active uncontrolled infection [such as infection that requiring intravenous antibiotic therapy, human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, etc.]; Note: If hepatitis B virus surface antigen (HBsAg) is positive, HBV-DNA < 1000 cop/ml, and ALT/AST ≤ 2.0 × ULN can be included. HCV infection is defined as HCV-Ab positive.
• Have past history of or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung function, etc;
• Have undergone major surgery or have not recovered from the invasive operation within 4 weeks before taking the study drug for the first time and are not suitable for the clinical trial according to the judgment of the investigators;
• Who is participating in other clinical studies or have participated in other intervention clinical trials within 4 weeks before screening;

Where it is running

• Peking University Third Hospital — Beijing, Beijing Municipality, China (enrolling)
• Fudan University Shanghai Cancer Center — Shanghai, Shanghai Municipality, China (enrolling)
• West China Hospital，Sichuan University — Chengdu, Sichuan, China (enrolling)
• Cancer Hospital, Chinese Academy of Medical Sciences — Beijing, Beijing Municipality, China

Full record on ClinicalTrials.gov

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