Indolent B-Cell Non-Hodgkin Lymphoma MedDRA version: 20.0 Level: PT Classification code 10029601 Term: Non-Hodgkin's lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Zydelig
Product Name: Idelalisib
Product Code: IDELA, GS-1101
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: I
Sponsors
Gilead Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients must meet all of the following conditions to be eligible for enrollment into the study: 1. Age =18 years. 2. Karnofsky performance score of =60 (Eastern Cooperative Oncology Group [ECOG] performance score of 0, 1, or 2). 3. Histologically confirmed diagnosis of B-cell iNHL, with histological subtype limited to the following based on criteria established by the World Health Organization (WHO) 2008 classification of tumors of haematopoietic and lymphoid tissues: - Follicular lymphoma (FL) Grade 1, 2, or 3a - Small lymphocytic lymphoma (SLL) with absolute lymphocyte count 2 cm in the longest dimension [LD] and =1.0 cm in the longest perpendicular dimension [LPD] as assessed by CT or MRI) 6. Prior treatment with =2 prior chemotherapy- or immunotherapy-based regimens for iNHL. 7. Prior treatment with rituximab and with an alkylating agent (eg, bendamustine, cyclophosphamide, ifosfamide, chlorambucil, melphalan, busulfan, nitrosoureas) for iNHL. 8. Lymphoma that is refractory to rituximab and to an alkylating agent. Please refer to Study Protocol section 4.1.1 for the definition of refractoriness. 9. Discontinuation of all other therapies (including radiotherapy or chemotherapy) for the treatment of iNHL =3 weeks before initiation of study treatment (Visit 2). 10. All acute toxic effects of any prior antitumor therapy resolved to Grade =1 before initiation of study treatment (Visit 2) (with the exception of alopecia [Grade =2 permitted], neurotoxicity [Grade =2 permitted], or bone marrow parameters noted in Table 1 of protocol section 4.1.1 [Grade =2 permitted]). 11. Required baseline laboratory data (within 4 weeks prior to start of study drug administration) as shown in Table 1 (see Study Protocol section 4.1.1). 12. For men and women of childbearing potential (ie, patients who are not postmenopausal or surgically sterile), willingness to abstain from sexual intercourse or employ an effective method of contraception during the study drug administration and follow-up periods. 13. Willingness and ability to provide written informed consent and to comply with scheduled visits, drug administration plan, imaging studies and contrast dye administration, laboratory tests, other study procedures, and study restrictions. 14. Evidence of a personally signed informed consent indicating that the patient is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, possible side effects, potential risks and discomforts, and other pertinent aspects of study participation.
Exclusion criteria
Exclusion criteria: The presence of any of the following conditions will exclude a patient from study enrollment: 1. Central nervous system or leptomeningeal lymphoma. 2. Known histological transformation from iNHL to diffuse large B-cell lymphoma. 3. History of a non-lymphoma malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for =5 years. 4. Evidence of ongoing systemic bacterial, fungal, or viral infection (excluding viral upper respiratory tract infections) at the time of initiation of study treatment (Visit 2). 5. Pregnancy or breastfeeding. 6. Ongoing alcohol or drug addiction. 7. Known history of drug-induced liver injury, chronic active HCV, chronic active HBV, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, ongoing extrahepatic obstruction caused by stones, cirrhosis of the liver or portal hypertension. 8. History of prior allogeneic bone marrow progenitor cell or solid organ transplantation. 9. Ongoing immunosuppressive therapy, including systemic corticosteroids. 10. Prior therapy with CAL-101 11. Exposure to another investigational drug within 3 weeks prior to start of study treatment. 12. Concurrent participation in another therapeutic treatment trial. 13. Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, ECG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism or excretion of the study drug; or impair the assessment of study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate tumor regression as determined by ORR in patients receiving Idelalisib for treatment of iNHL refractory to rituximab and alkylating agents;Primary end point(s): ORR – defined as the proportion of patients who achieve a confirmed complete response (CR) or partial response (PR or MR for subjects with WM) during Idelalisib treatment; response definitions will be based on standard criteria [Cheson 2007]; Secondary Objective: - To determine the onset, magnitude, and duration of tumor control and of treatment success in patients receiving Idelalisib - To characterize HRQL as reported by patients with iNHL receiving Idelalisib - To evaluate the effects of Idelalisib on patient performance status - To assess the pharmacodynamic effects of Idelalisib - To evaluate Idelalisib treatment administration and compliance with Idelalisib therapy - To describe the safety profile of Idelalisib - To characterize Idelalisib plasma exposure over time - To generate pharmacokinetic data with the final tablet formulation of Idelalisib in patients with iNHL (through conduct of a pharmacokinetic sub-study) ; Timepoint(s) of evaluation of this end point: A single formal interim analysis is planned solely to determine if there is a sufficient ORR observed early in the study to warrant continuing the study to completion. At the latest, the interim analysis will be completed once 31 patients have been enrolled and completed the 16-week tumor assessment. The final study analysis will be performed when all enrolled patients have completed efficacy, safety, and other assessments through 24 weeks of evaluation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - DOR – defined as the interval from the first documentation of CR or PR (or minor response MR for subjects with WM) to the earlier of the first documentation of disease progression or death from any cause -Lymph node response rate (LNR) – defined as the proportion of subjects who achieve a =50% decrease from baseline in the sum of the products of the greatest perpendicular diameters (SPD) of index lymph nodes - TTR – defined as the interval from the start of Idelalisib treatment to the first documentation of CR or PR (or MR for subjects with WM) - PFS – defined as the interval from the start of Idelalisib treatment to the earlier of the first documentation of disease progression or death from any cause - Changes in HRQL as reported by patients using the FACT-Lym (Appendix C of protocol) - Changes in performance status as documented using the Karnofsky performance criteria (Appendix D of protocol) - Changes in the plasma concentrations of disease-associated chemokines and cytokines - Overall safety profile of Idelalisib characterized by the type, frequency, severity, timing, and relationship to study therapy of any adverse events or abnormalities of physical findings, laboratory tests, or ECGs; drug discontinuations due to adverse events; or serious adverse events - Study drug administration as assessed by prescribing records and compliance as assessed by quantification of used and unused drug - Idelalisib trough and peak plasma concentrations assessed pre-dose and 1.5 hours post-dose - Pharmacokinetic parameters (eg, Tmax, Cmax, trough concentration [Ctrough], AUC) (for patients in pharmacokinetic sub-study) ;Timepoint(s) of evaluation of this end point: The final study analysis will be performed when all enrolled patients have completed efficacy, safety, and oth | — |
Countries
France, Germany, Italy, Poland, Switzerland, United Kingdom, United States
Contacts
Public ContactClinical Trial Mailbox
Gilead Sciences International Ltd.
Outcome results
None listed