Ann Arbor Stage II Follicular Lymphoma, Ann Arbor Stage III Follicular Lymphoma, Ann Arbor Stage IV Follicular Lymphoma, Grade 1 Follicular Lymphoma, Grade 2 Follicular Lymphoma, Grade 3a Follicular Lymphoma
Conditions
Brief summary
This is a single center, open label, single arm phase II clinical trial. The objective of this study is to assess the feasibility and efficacy of zanubrutinib combined with venetoclax and Rituximab in patients with previously untreated follicular lymphoma (FL) .
Detailed description
Follicular lymphoma (FL)is the most common inert non Hodgkin's lymphoma (iNHL). Their natural courses are slow but highly variable. The standard first-line treatment of advanced FL is based on rituximab. Whether combined with chemotherapy or not, it can induce lasting remission, but it is usually incurable. Although the first-line immunochemotherapy regimen has high efficacy, it also has high toxicity. Cytotoxic chemotherapy is related to many side effects, including bone marrow suppression and immunosuppression, gastrointestinal and cardiac toxicity, neurotoxicity and the occurrence of secondary tumors. About 20% of FL patients relapse within 2 years after first-line chemotherapy. The overall prognosis of these patients is poor. This clinical trial aims to evaluate the feasibility and efficacy of free-chemotherapy regimen (zanubrutinib combined with venetoclax and Rituximab) in patients with previously untreated follicular lymphoma.
Interventions
DRUGZanubrutinib
BTK inhibitor
BIOLOGICALRituximab
Monoclonal antibody to CD20
DRUGVenetoclax
BCL-2 inhibitor
Sponsors
Chinese PLA General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* A diagnosis of follicular lymphoma (grades 1, 2, or 3a), untreated. * Stage II, III, or IV disease. * Able and willing to provide written informed consent and to comply with the study protocol. * at least one measurable disease. * Must be in need of therapy as evidenced by at least one of the following criteria: * Presence of at least one B symptom: Fever (\> 38 Celsius \[C\]) not due to infectious etiology, or Night sweats, or Weight loss \> 10% in the past 6 months; * Fatigue due to lymphoma; * Splenomegaly (\> 13 cm); * Compression syndrome (ureteral, orbital, gastrointestinal); * Any of the following cytopenias, due to lymphoma: Hemoglobin ≤ 10 g/dL, or Platelets ≤ 100 x 10\^9/L, or Absolute neutrophil count (ANC) \< 1.5 x 10\^9/L; * Pleural or peritoneal effusion; * Lactate dehydrogenase (LDH) \> upper limit of normal (ULN) or beta (B)2 microglobulin \> ULN; * Other lymphoma-mediated symptoms as determined by the treating physician. * ECOG ≤ 2 * ANC \> 1.0 x 10\^9/L (for patients without bone marrow involvement by lymphoma) * Platelet count \> 50 x 10\^9/L (for patients without bone marrow involvement by lymphoma) * Prothrombin time (PT)/international normal ratio (INR) \< 1.5 x (upper limit of normal) ULN and partial thromboplastin time (PTT) (activated partial thromboplastin time \[aPTT\]) \< 1.5 x ULN (unless abnormalities are unrelated to coagulopathy or bleeding disorder). When treated with warfarin or other vitamin K antagonists, then INR ≤ 3.0) * Serum aspartate transaminase (AST) and alanine transaminase (ALT) \< 3 x ULN * Creatinine clearance \> 30 ml/min calculated by modified Cockcroft-Gault formula * Bilirubin \< 1.5 x ULN unless bilirubin is due to Gilbert's syndrome, documented liver involvement with lymphoma, or of non-hepatic origin, in which case bilirubin should not exceed 3 g/dL * Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[B-hCG\]) pregnancy test at screening. Women who are pregnant or breastfeeding are ineligible for this study
Exclusion criteria
* Known active central nervous system lymphoma or leptomeningeal disease * Follicular lymphoma with evidence of diffuse large B-cell transformation * Grade 3b follicular lymphoma * Any prior history of other malignancy besides follicular lymphoma * History of severe allergic or anaphylactic reactions to monoclonal antibody therapy * Patients who have undergone major surgery within 14 days * The researchers believe that it is not advisable for the participant to take part in this trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| CR rate | Within 6 months of therapy completion | Determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. The number and percentage of subjects with a CR will be tabulated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall response rate (ORR) | Within 6 months of therapy completion | CR + partial response (PR), determined by PET/CT based on Cheson, Lugano classification 2014 as assessed by the investigator. The number and percentage of subjects with an ORR will be tabulated. |
| Progression-free survival | up to two years | PFS is defined as the duration from date of treatment initiation to date of disease progression or death from any cause |
| Overall survival | up to two years | PFS is defined as the duration from date of treatment initiation to date of death from any cause |
| Incidence of Treatment-Emergent Adverse Events | Up to 90 days after the last dose of study drugs | Incidence of subjects occuring treatment related adverse events. |
Countries
China
Contacts
CONTACTYANG LIU, MD
Outcome results
None listed