| Eligibility |
Inclusion Criteria:1.Volunteer for clinical research; fully understand the study and sign
an informed consent (ICF); be willing to follow and be able to complete all study steps;
2.Histologically confirmed diffuse large B cell lymphoma (DLBCL), and CD20-positive
patients; 3.Age from 18 to 80 (patients with age > 80 and status score > 2 should be
assessed by the investigator to make sure whether they are suitable for this clinical
trail); 4.Relapse / refractory DLBCL, relapse or refractory disease is defined as: 1)
disease recurrence after complete remission (CR), 2) partial remission (PR), disease
stability (SD) or disease progression (PD) after the final treatment before the study;
patients who younger than 65 should be treated with at least two different chemotherapy
regimens, and patients age> 65 need at least one chemotherapy regimen, or relapse after
remission; 5.Patiens have measurable lesions, the standard is showed in Appendix 1; 6.ECOG
score is no more than 2; 7.The expected survival period is greater than 3 months;
8.Adequate organ and bone marrow function, no severe hematopoietic dysfunction, no cardiac,
lung, liver, kidney, thyroid dysfunction, or immune deficiency (no blood transfusion,
granulocyte colony stimulating factor, or other medical support drugs within 7 days prior
to the start of this study) : neutrophil absolute count (ANC) =1.0×109/L, platelet (PLT)
=50×109/L, hemoglobin >80 g/L, aspartate aminotransferase (AST/SGOT) and alanine
aminotransferase (ALT/SGPT) =2.5×ULN, total bilirubin (TBIL) =1.5×ULN, creatinine clearance
(Ccr) =40ml/min (estimated by Cockcroft-Gault formula), international standardized ratio
(INR) =1.5×ULN, prothrombin time (PT) and activated partial thrombin time (APTT) =1.5×ULN
(unless the subject is receiving anticoagulant therapy at screening time); 9.Patiens will
be enrolled only after the toxicity of the previously treated return to «the Common
Terminology Criteria for Adverse Events» (CTCAE) V 5.0 score<1. Irreversible toxicity
caused by previous antitumor treatment and is not expected to worsen than grade 2 toxicity
(e. g. thrombocytopenia, anemia, neurotoxicity, hair loss and hearing loss, during the
study) should be evaluated by the investigator; 10.Patiens who do not meet the criteria for
ASCT or who refuse ASCT. Patiens who relapse after ASCT can be enrolled at least 100 days
after the transplantation.
11.Before starting treatment, two pregnancy tests (at least one of them should be a
serological pregnancy test) should be performed and the result must be negative.The first
test must be conducted within 10-14 days before lenalidomide treatment, and the second test
should within 24 hours before lenalidomide treatment.
12.Fertile women must agree to use reliable contraception from 4 weeks before lenalidomide
treatment to at least 90 days after the last administration of zanubrutinib and
lenalidomide, or 12 months after the last administration of rituximab (whichever is longer
as the standard). Male patients taking the study drug may not donate sperm throughout the
study.
13.Patients are not allowed to donate blood during lenalidomide treatment and within 4weeks
after withdrawal, as blood may be used in pregnant female patients whose fetus will not be
exposed to lenalidomide.
Exclusion Criteria:1.Special type of lymphoma: primary mediastinal (thymus) large B cell
lymphoma.
2.Patients with other hematological diseases and non-lymphoma were diagnosed. 3.Other
active malignancies that require concurrent treatment. 4.Major surgery is performed within
4 weeks before screening. 5.Previous anticancer therapy toxicity is still equal to or more
than grade 2 when enrol (except for alopecia, ANC, hemoglobin and platelet toxicity); ANC,
hemoglobin and platelet-related requirements, please follow the inclusion criteria 9.
6.History of other active malignant diseases within 2 years prior to study entry, but the
following situation are eligibility for inclusion: 1) adequately treated carcinoma in situ
of the cervix; 2) Local basal cell carcinoma or squamous cell carcinoma of the skin; 3)
Pre-existing malignant disease that has been controlled and treated locally and radically
(surgically or otherwise).
7.Have clinically significant cardiovascular disease, including: 1) myocardial infarction
that occurred within 6 months prior to screening stage; 2) Unstable angina pectoris within
3 months before screening stage; 3) Clinical major arrhythmia (e.g., persistent ventricular
tachycardia, ventricular fibrillation, tachycardia with torsional tip); 4) QTcF (corrected
according to Fridericia formula) >480 msec; 5) History of second-degree type II
atrioventricular block or third-degree ATrioventricular block; 6) Class III or IV
congestive heart failure as defined by the New York Heart Association (NYHA).
8.History of severe hemorrhagic disease, such as hemophilia A, hemophilia B, von willebrand
disease, or history of spontaneous bleeding requiring blood transfusion or other medical
intervention.
9.History of stroke or intracranial hemorrhage within 6 months prior to the first taking of
the investigational drug.
10.Inability to swallow capsules or a medical condition that significantly affects
gastrointestinal function, such as malabsorption syndrome, gastrectomy or small bowel
resection, symptomatic inflammatory bowel disease, or partial or complete intestinal
obstruction; 11.Uncontrolled systemic infection requiring intravenous administration of
drugs for parenteral anti-infective therapy.
12.Human immunodeficiency virus (HIV) infection, or presence of serological status of
active hepatitis B or C virus infection: 1)Either hepatitis B surface antigen (HBsAg)
positive or hepatitis B core antibody (HBcAb) positive serology can be enrolled if
hepatitis B virus (HBV) DNA (<20 IU/mL) and are willing to receive monthly HBV reactivation
monitoring. 2) For patients in the presence of hepatitis C virus antibody, they could be
enrolled if HCV RNA is not detected.
13.Hypersensitivity is known to either lenalidomide or rituximab, or to chemical or
biological analogues of lenalidomide and rituximab.
14.Women during pregnancy or lactation. 15.Any life-threatening disease, medical condition,
or incomplete organ system as considered by the investigator that may affect the safety of
the subject or lead to the study risk.
16.History of deep venous thrombosis (DVT) or pulmonary embolism (PE) in the past 12
months.
-
|
