Trial of Idelalisib in Patients With Relapsed Diffuse Large B-cell Lymphoma (ILIAD)

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

Based on the high response rate in heavily pretreated patients with indolent B-cell lymphomas, among which it is likely that many have undetected transformed disease, the investigators hypothesize that idelalisib may also be active in relapsed DLBCL, particularly of the GCB subtype. Possibly, the efficacy may be related to the presence of specific mutations within the B-cell receptor pathway.

Study Overview

• Status: Completed
• Conditions: Diffuse Large B Cell Lymphoma
• Intervention / Treatment: Drug: Idelalisib

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Aarhus C, Denmark, 8000
    • Aarhus University Hospital
  • Odense, Denmark
    • Odense University Hospital
• Sweden
  • Halmstad, Sweden, 30 233
    • Halmstad County Hospital
  • Linköping, Sweden, 581 85
    • Linköping University Hospital
  • Lund, Sweden, 221 85
    • Skåne University Hospital
  • Stockholm, Sweden, 141 86
    • Karolinska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age >18 years.

2. Histologically confirmed diffuse large B-cell lymphoma (DLBCL) , including transformed low grade lymphoma, with either:

   1. Refractory disease: defined as disease progression while receiving their most recent prior cytotoxic chemotherapy (single-agent immunotherapy as maintenance is not considered cytotoxic therapy).
   2. Persistent disease: defined as stable disease or partial response at the completion of their most recent prior cytotoxic chemotherapy.
   3. 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. The use of highly-effective contraception methods* are required during the study for women of child-bearing potential. Due to the toxicity of idelalisib, women who will use a hormonal contraceptive must in addition also use a barrier method, since it is currently unknown whether idelalisib may reduce the effectiveness of hormonal contraceptives. 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.

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment arm; Idelalisib 150 mg x 2 p o, until progression	Drug: Idelalisib; Idelalisib 150 mg x 2 p o

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall response rate for GCB DLBCL	Overall response rate (ORR) for GCB DLBCL	at time of progression, up to 112 weeks from start of treatment

Collaborators and Investigators

• Sponsor: Nordic Lymphoma Group
• Investigators: Principal Investigator: Mats Jerkeman, Department of Oncology Skåne University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 7, 2017
• Primary Completion (ACTUAL): September 30, 2021
• Study Completion (ACTUAL): September 30, 2021

Study Registration Dates

• First Submitted: April 30, 2018
• First Submitted That Met QC Criteria: July 2, 2018
• First Posted (ACTUAL): July 3, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 13, 2021
• Last Update Submitted That Met QC Criteria: October 12, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Idelalisib
• Other Study ID Numbers: NLG-LBC-07

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No