relapsed and refractory follicular lymphoma
Conditions
Interventions
Experimental group:Duvelisib
Sponsors
Ruijin Hospital, Shanghai Jiaotong University School of Medicine
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Subjects must have been fully informed about the study and signed the informed consent form (ICF). 2. Aged 18 years or older. 3. Subjects who have been diagnosed with FL by histopathological and/or cytological examination, and had received at least 2 prior lines of therapy. (Subjects must undergo histopathological and/or cytological examination during the screening period and must agree to provide tumor tissue sections or fresh tumor tissue to central laboratory for pathological review. For special cases, if a subject has a high risk during the procedure of a puncture for biopsy, in the investigators judgement, the subject could provide previous pathology reports and tumor tissue sections/tumor tissue instead). 4. Relapsed is defined as: progressive disease (PD) after a full course of treatment with at least one regimen containing rituximab. Refractory is defined as: Lack of a CR or PR after a full course of chemotherapy in combination with rituximab or single-agent rituximab; or PD during, or within 6 months of the last dose of the above treatment. A full course of treatment containing rituximab is defined as: completion of >= 4 cycles chemotherapy in combination with rituximab, or >= 4 clinically recommended dose of single-agent rituximab, according to pathological classification and lymphoma stage. The definition of PD during treatment requires: when PD occurs during in induction therapy, it will require completion of at least one cycle chemotherapy in combination with rituximab or single-agent rituximab; when PD occurs during maintenance therapy, it will require completion of at least one dose of rituximab treatment. Response is defined as CR and PR. 5. At least one lesion meets the requirement of evaluable or measurable lesion in the Lugano 2014 criteria. [Evaluable lesion refers to the 18FDG/PET intake of lymph node or extranodal lesion higher than liver, and features showed in the PET and/or CT imaging are consistent with lymphoma; Measurable lesion refers to the long axis of a lymph node > 1.5 cm, or long axis >1.0-1.5 cm but short axis > 1.0 cm, or longest diameter of a extranodal lesion > 1.0 cm (if the only measurable lesion had been previously treated with radiotherapy, evidence of radiographic progression after the radiotherapy will be required).] 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-2 (corresponds to Karnofsky Performance Status [KPS] >= 60%). 7. At least 3 months expected survival. 8. Adequate renal and hepatic function, and the laboratory tests need to meet the following requirements: a. Serum creatinine <=2 * upper limit of normal (ULN); b. Total bilirubin <= 1.5 * ULN; c. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels <= 3 * ULN. 9. The toxicity of the previous antitumor therapy returned to <= Grade 1 (except alopecia). 10. Negative serum or urine human chorionic gonadotropin (HCG) pregnancy test of subjects who are women of childbearing potential (except menopause and hysterectomy). Male and female subjects of childbearing potential are willing to use medically acceptable methods of birth control for the duration of the study, including 30 days after the last dose of duvelisib. 11. Ability to adhere to the study visit schedule and all protocol requirements.
Exclusion criteria
Exclusion criteria: Subjects are to be excluded from the study if they meet any of the following criteria: 1. Grade 3B FL or clinical evidence of transformation to a more aggressive subtype of lymphoma. 2. Known hypersensitivity to the study drug or excipients. 3. Prior treatment with any PI3K inhibitor or Brutons Tyrosine Kinase (BTK) inhibitor. 4. Prior history of allogeneic hematopoietic stem cell transplant (HSCT), or autologous hematopoietic stem cell transplant within 6 months before first dose of study drug. 5. Administration of medications or foods that are strong inhibitors or inducers of CYP3A within 2 weeks prior to the first dose of study drug. 6. Major surgery within 4 weeks before the first dose of study drug, or no recovery from an invasive procedure. 7. Prior antitumor therapy within 4 weeks before the first dose of study drug, including chemotherapy, immunotherapy, radiotherapy, or other investigational agents (or washout period is less than 5 half-lives of the previous used antitumor drugs if the washout period is less than 4 weeks). 8. Ongoing treatment with chronic immunosuppressants (e.g. cyclosporine) or systemic steroids >20 mg prednisone (or equivalent) once daily (QD). 9. Central nervous system (CNS) lymphoma. The subjects with symptomatic CNS disease must undergo a CT scan or diagnostic lumbar puncture prior to administration of study drug, with a positive result. 10. Ongoing systemic bacterial, fungal, or viral infections at the time of initiation of study treatment, which is defined as requiring therapeutic dosing of an antimicrobial, antifungal or antiviral agent. (Subjects on antimicrobial, antifungal or antiviral prophylaxis are not specifically excluded if all other inclusion/exclusion criteria are met and there is no presence of active infection). 11. Human immunodeficiency virus (HIV) infection. 12. Active macrophage virus (CMV) or Epstein-Barr virus (EBV) infection (positive results of viral load). 13. Baseline QTcF >500 ms (average of triplicate readings). This criterion does not apply to subjects with a right or left bundle branch block. 14. Active hepatitis B virus infection (with positive result for hepatitis B virus surface antigen and hepatitis B virus DNA over 1000 copies/mL), or active hepatitis C virus infection (with hepatitis C virus RNA over 1000 copies/mL). 15. Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV) or herpes zoster (VZV) at time of initiation of study treatment. 16. History of chronic liver disease, veno-occlusive disease/sinus obstruction syndrome, alcohol abuse or illicit drug use. 17. History of interstitial lung disease of any severity and/or severely impaired lung function. 18. History of drug-induced colitis or drug-induced interstitial pneumonitis. 19. History of tuberculosis treatment within 2 years prior to the first dose of study drug. 20. Unstable or severe uncontrolled medical condition (e.g., unstable cardiac function, unstable pulmonary condition), and any uncontrolled medical illness that would, in the investigators judgment, increase the subjects risk to participate in this study. 21. Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix; bladder cancer or prostate cancer not requiring treatment. Subjects with previous malignancies are eligible if they have been disease free for 2 years or more. 22. History of stroke, unstable angina, myocardial infarction, or ventricular arrh
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR), with overall response defined as best response of complete response/remission (CR) or partial response/remission (PR), assessed by Independent Review Committee (IRC) according to the revised International Working Group Criteria (Cheson 2007 Criteria); | — |
Secondary
| Measure | Time frame |
|---|---|
| ORR assessed by study center according to the Cheson 2007 Criteria;ORR assessed respectively by IRC and study center, according to the revised Lugano Guidelines (Lugano 2014 Criteria);Treatment-emergent adverse events (TEAEs), ECG measures, and changes in safety laboratory values;Duration of response (DOR);Progression-free survival (PFS);Overall survival (OS) ;Time to response (TTR);PK of duvelisib and its metabolite(s); the correlation between exposure level of them and the efficacy/safety in all the subjects; | — |
Countries
China
Contacts
Public ContactXiugao Yang
Outcome results
None listed