Relapsed/refractory diffuse large B-cell lymphoma, including transformed low grade lymphoma. MedDRA version: 20.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851
Conditions
Interventions
Trade Name: Zydelig
Product Name: Zydelig
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: IDELALISIB
CAS Number: 870281-82-6
Concentration unit: mg milligram(s)
Concentration type: range
Sponsors
Nordic Lymphoma Group
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age >18 years. 2. Histologically confirmed diffuse large B-cell lymphoma (DLBCL) , including transformed low grade lymphoma, with either: a. Refractory disease: defined as disease progression while receiving their most recent prior cytotoxic chemotherapy (single-agent immunotherapy as maintenance is not considered cytotoxic therapy). b. Persistent disease: defined as stable disease or partial response at the completion of their most recent prior cytotoxic chemotherapy. c. Relapsed/recurrent disease: defined as complete response at the end of their most recent prior cytotoxic chemotherapy with subsequent relapse or disease recurrence. 3. Subjects must have received prior rituximab and may have received up to 5 prior regimens containing cytotoxic chemotherapies. 4. Subjects must not be candidates for high-dose chemotherapy with autologous stem cell support (ASCT), due to one or more of the following factors: relapse after high dose chemotherapy, age, comorbid disease, performance status, or persisting toxicities from prior chemotherapy. 5. Absolute neutrophil count (ANC) >1.0 x 109/L, unless related to bone marrow infiltration. 6. At least 1 measurable disease lesion that is >1.0 cm in 2 perpendicular dimensions, with the product diameter >2.25 cm2 by computed tomography (CT) or magnetic resonance imaging (MRI). 7. Negative serum pregnancy test within 1 week before first treatment if the subject is a woman of childbearing potential. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. 8. WHO performance status 0 – 3. 9. Written informed consent. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 24 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 48
Exclusion criteria
Exclusion criteria: 1. Prior allogeneic hematopoietic stem cell transplant (HSCT). 2. Prior treatment with PI3K inhibitors. 3. Serum total bilirubin = 1.5 x ULN (unless elevated due to Gilbert’s syndrome). 4. Serum ALT and AST ? 2.5 x ULN. 5. Estimated Creatinine Clearance 2 years. 16. Previous myocardial infarction or pulmonary hypertension <6 months before first dose of investigational product. 17. History of clinically significant ventricular arrhythmia, prolonged QTc interval or unexplained syncope. 18. Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of idelalisib in patients with relapsed/refractory diffuse large B-cell lymphoma.;Secondary Objective: - To evaluate the efficacy od idelalisib in relapsed/refractory diffuse large B-cell lymphoma in term of overall response rate in relation to cell-of-origin and specific mutations. - To evaluate the efficacy of idelalisib in diffuse large B-cell lymphoma in terms of progression-free survival, complete remission rate, response duration and overall survival. - To evaluate safety of idelalisib in diffuse large B-cell lymphoma. ;Primary end point(s): Overall response rate for the Germinal Center B-cell (GCB) subtype of diffuse large B-cell lymphoma.;Timepoint(s) of evaluation of this end point: Respons is evaluated at week week 8, week 16, week 24, week 36, week 48, week 60, week 72, week 84, week 96 and at week 108. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall response rate (ORR) for the non-GCB subtype of diffuse large B-cell lymphoma. 2. Progression-free survival 3. Complete remission rate 4. Response duration 5. Overall survival 6. Evaluation of specific mutations affecting pathways downstream of B-cell receptor signalling (including CD79a, CD79b, MYD88, CARD11) as possible biomarkers for efficacy 7. Toxicity 8. Health-related quality of Life ;Timepoint(s) of evaluation of this end point: Toxicity and overall survival is evaluated continously during study treatment. Quality of live is evaluated at baseline, week 16, week 36, and at week 72. Respons is evaluated at week 8, week 16, week 24, week 36, week 48, week 60, week 72, week 84, week 96 and at week 108. Biomarkers for efficacy will be analysed partly during the study, and also after study end. | — |
Countries
Denmark, Sweden
Contacts
Public ContactKarin Fjordén
Skåne University Hospital, Department of Oncology
Outcome results
None listed