Recruiting PHASE1 Lymphoma, B-Cell

New treatment option for Lymphoma, B-Cell

Official title Phase Ib Clinical Study of Keynatinib

ClinicalTrials.gov ID: NCT04807881

What this study is testing

What is Keynatinib?

Keynatinib is an investigational medicine, given as a twice-daily, being studied as a potential treatment for lymphoma, b-cell.

Also referred to as TL007.

Plain-language explanation of the investigational treatment - it is being studied and is not an approved or proven therapy. The study team can confirm the details.

What it's testing: 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.

Phase 1: an early, usually small safety study

A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.

Who can take part

Ages 18 and older

You may be able to join 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;

You likely can't join 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...
Have previously received the treatment of B Cell Receptor (BCR) inhibitors (such as BTK, phosphoinositide kinase 3 kinase [PI3K] or SYK inhibitors)...
Have received Allogenetic Haematopoietic Stem Cell Transplantation (Allo-HSCT) or other organ transplants (except for those who have received ASCT...

See the full eligibility criteria

Who can join

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...
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;
people 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...
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...
Coagulation function: International Standardized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN-Cohort 1/2/3;
Fertile female people must agree to use contraceptives with an annual failure rate of \< 1% or maintain abstinence (avoid heterosexual intercourse) during the study and at least 90 days after the last administration of...

What rules you out

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...
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...
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...
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...
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...
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)...
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...
Who is participating in other clinical studies or have participated in other intervention clinical trials within 4 weeks before screening;
Have history of alcohol or drug abuse;
Pregnant or lactating women;
Concomitant administration of drugs with moderate to severe inhibition or strong induction of cytochrome P450 CYP3A
people determined by the investigators to be unsuitable for other reasons; Cohort 2: R/R-CLL/SLL
Have medical history of prolymphocytic leukemia, known medical history of Richter syndrome or currently suspected Richter transformation (patients with clinical suspicion need biopsy to exclude transformation)
Have previously received any of the following treatments:
Chemotherapy, targeted therapy, radiotherapy or antibody-based anti-tumor therapy within 4 weeks or 5 half-lives (whichever is shorter) before the first administration;
Previous treatment with 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 treatment with bispecific...
Patients who received allogeneic hematopoietic stem cell transplantation (Allo-HSCT) or other organ transplantation within the past 6 months;
Patients who received autologous hematopoietic stem cell transplantation within the past 6 months;
Use of systemic corticosteroids within 7 days before the first administration of study drug, or continuous use of prednisone at or above 20 mg/day or equivalent;
Other malignancies within 3 years, except for curable basal or squamous cell skin cancer, superficial bladder cancer, and carcinoma in situ of the uterine 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...
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) being applied that will be reasonably tolerable and sufficient for more than one...
Have active bleeding within 2 months before screening or is taking anticoagulant/antiplatelet drugs, or the investigators believe that there is a clear bleeding tendency (such as esophageal varices with bleeding risk...
Active and/or persistent autoimmune anemia and/or autoimmune thrombocytopenia requiring treatment (e.g., idiopathic thrombocytopenic purpura);
Have medical history of deep vein thrombosis or pulmonary embolism;
Have medical history of stroke or intracranial hemorrhage within 6 months before taking study drug;
Have clinically significant gastrointestinal abnormalities, which might affect drug intake, transport or absorption (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.);
Have active infection requiring systemic anti-infective treatment;
At screening, patients with active uncontrolled infection [such as intravenous infection that requiring antibiotic therapy, human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV)...
Have past history of or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung function, etc;
Have history of alcohol or drug abuse;
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...
Whowill participating in other clinical studies or haveparticipated in other intervention clinical trials within 4 weeks before screening;
Pregnant or lactating women;
Concomitant administration of drugs with moderate to severe inhibition or strong induction of cytochrome P450 CYP3A;
people determined by the investigators to be unsuitable for other reasons; Cohort 3: R/R-MCL
Havepreviously received any of the following treatments:
Chemotherapy, targeted therapy, radiotherapy or antibody based anti-tumor therapy are used within the first 4 weeks or 5 half-lives (whichever is shorter) before the first administration;
Have previously received the treatment of 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 received...
Use of systemic corticosteroids at or above 20 mg/day prednisone or equivalent within 7 days before the first administration of study drug;
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...
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...
Have medical history of deep vein thrombosis or pulmonary embolism;
Have medical history of stroke or intracranial hemorrhage within 6 months before taking study drug;
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)...
Have past history of or current pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe impairment of lung function, etc;
Have history of alcohol or drug abuse;
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 is not suitable for the clinical trial according to the judgment of the...
Who is participating in other clinical studies or have participated in other intervention clinical trials within 4 weeks before screening;
Pregnant or lactating women;
Concomitant administration of drugs with moderate to severe inhibition or strong induction of cytochrome P450 CYP3A;
people determined by the investigators to be unsuitable for other reasons;

The study team makes the final eligibility decision.

Where it's taking place

Beijing, Beijing Municipality, China
Shanghai, Shanghai Municipality, China
Chengdu, Sichuan, China

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18 years and older. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include Beijing, Beijing Municipality, China; Shanghai, Shanghai Municipality, China; Chengdu, Sichuan, China. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from ClinicalTrials.gov; the study team decides eligibility.