A Phase II Trial of Idelalisib in Patients with Relapsed/Refractory Diffuse Large B-cell Lymphoma.

Phase 1

Conditions: Relapsed/refractory diffuse large B-cell lymphoma, including transformed low grade lymphoma.
MedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2016-001058-16-DK

Lead Sponsor: ordic Lymphoma Group

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 36

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

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 < 10 ml/min.
6.Known seropositivity for human immunodeficiency virus (HIV).
7.Known history of drug induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease,
non- alcoholic steatohepatitis, primary biliary cirrhosis, on-going extra-hepatic obstruction caused by cholelithiasis, cirrhosis of the liver
or portal hypertension.
8.Known history of drug induced pneumonitis.
9.On-going inflammatory bowel disease.
10.Evidence of serious active infection (eg, requiring an intravenous [IV] antibiotic, antiviral, or antifungal agent), or subjects with a
recent history of deep tissue infections such as fascitis or osteomyelitis.
11.Chemotherapy, cancer immunosuppressive therapy, growth factors (except erythropoietin), or investigational drugs/devices
<10 days before first dose of investigational product in this study. Subjects receiving high doses of corticosteroids must have been
tapered to a stable dose
at least 7 days before the first dose of investigational product.
12.Pregnant or breastfeeding women.
13.Symptomatic central nervous system (CNS) NHL; a lumbar puncture is not required unless CNS involvement with NHL is clinically suspected.
14.Unstable or severe uncontrolled medical condition (eg, unstable cardiac function, unstable pulmonary condition).
15.Concurrent active malignancy other than nonmelanoma skin cancer or carcinoma in situ of the cervix. Subjects with previous
malignancies are eligible provided that they have been disease free for >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.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy of idelalisib in patients with relapsed/refractory 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 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<br> and specific mutations.<br>- To evaluate the efficacy of idelalisib in diffuse large B-cell lymphoma in terms of progression-free survival, complete remission rate, response<br> duration and overall survival.<br>- To evaluate safety of idelalisib in diffuse large B-cell lymphoma.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1.Overall response rate (ORR) for the non-GCB subtype of diffuse large B-cell lymphoma.<br>2.Progression-free survival<br>3.Complete remission rate<br>4.Response duration<br>5.Overall survival<br>6.Evaluation of specific mutations affecting pathways downstream of B-cell receptor signalling (including CD79a, CD79b, MYD88, CARD11) <br> as possible biomarkers for efficacy<br>7.Toxicity<br>8.Health-related quality of Life<br>;Timepoint(s) of evaluation of this end point: Toxicity and overall survival is evaluated continously during study treatment.<br>Quality of live is evaluated at baseline, week 16, week 36, and at week 72.<br>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.<br> Biomarkers for efficacy will be analysed partly during the study, and also after study end.

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