Diffuse Large B-Cell Lymphoma, Mediastinal B-cell Lymphoma
Conditions
Brief summary
The primary objectives of this study are to evaluate safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of idelalisib; and to establish recommended phase 2 doses (RP2D) of idelalisib in combination with rituximab, ifosfamide, carboplatin, etoposide (RICE) in children and adolescents with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) or mediastinal B-cell lymphoma (MBCL)
Interventions
DRUGIdelalisib
Tablet (s) or dispersible tablets for suspension administered orally twice daily
DRUGRituximab
375 mg/m\^2 administered intravenously
DRUGIfosfamide
3 mg/m\^2 administered intravenously
DRUGCarboplatin
635 mg/m\^2 administered intravenously
DRUGEtoposide
100 mg/m\^2 administered intravenously
Sponsors
Gilead Sciences
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Histologically confirmed diagnosis of DLBCL or MBCL established by the World Health Organization (WHO) 2008 classification of tumors of hematopoietic and lymphoid tissues * Relapsed or refractory disease * Measurable or evaluable disease based on imaging or bone marrow examination * Karnofsky ≥ 60% for participants \> 16 years of age or Lansky ≥ 60 for participants ≤ 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score. * A negative serum pregnancy test is required for females of child bearing potential. * Participants of child bearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception . * Lactating females must agree to discontinue nursing before idelalisib is administered * Adequate bone marrow function as defined in the protocol * Adequate renal function as defined in the protocol Key
Exclusion criteria
* Prior ifosfamide, carboplatin, etoposide (ICE) therapy, with or without an anti-CD20 antibody, or history of hypersensitivity to any components of RICE * Known active central nervous system or leptomeningeal lymphoma or within 4 weeks from the last intrathecal therapy prior to the required diagnostic lumbar puncture (LP) for this study * Disease progression within 6 months from last anti-CD20 therapy * Ongoing toxicity from prior cytotoxic therapy (last dose at least 3 weeks prior to study entry) * Less than 4 half-lives from the last dose of previous targeted therapy and ongoing acute toxicity of prior targeted therapy * Active infection with human immunodeficiency virus (HIV), cytomegalovirus (CMV), hepatitis B virus (HBV), or hepatitis C virus (HCV) based on screening serology and polymerase chain reaction (PCR) results * Evidence of systemic bacterial, fungal, or viral infection at the time of treatment start (Day 1) * Ongoing or history of drug-induced pneumonitis * Ongoing or history of inflammatory bowel disease * Pregnancy or breastfeeding * Currently receiving other anti-cancer or other investigational drug * Prior solid organ transplantation * Prior allogeneic stem cell transplantation within 60 days or active acute graft versus host disease (GVHD) Grade 3 or higher * Known hypersensitivity to idelalisib, the metabolites, or formulation excipients * Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with the study requirements NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence Rate of Dose Limiting Toxicities (DLTs) | Up to Day 21 | DLTs refer to toxicities experienced during the first 21 days of study treatment that have been judged to be clinically significant and related to study treatment. |
| Proportion of Participants Experiencing Adverse Events (AEs) | Up to 12 months | — |
| Proportion of Participants Experiencing Serious Adverse Events (SAEs) | Up to 12 months | — |
| Proportion of Participants Experiencing Adverse Events (AEs) Leading to Idelalisib Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death | Up to 12 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) | Up to 12 months | Progression-Free Survival (PFS) is defined as the interval from the start date of RICE to the earlier of the first documentation of disease progression or death from any cause. Computed tomography/ magnetic resonance imaging (CT/MRI) scan at the conclusion of idelalisib monotherapy will serve as the reference for progression. |
| Pharmacokinetic Parameter: Cmax of Idelalisib | Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy | Cmax is defined as the maximum observed concentration of drug. |
| Pharmacokinetic Parameter: Cmax of GS-563117 | Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy | GS-563117 is the metabolite of idelalisib. Cmax is defined as the maximum observed concentration of drug. |
| Pharmacokinetic Parameter: Ctrough of Idelalisib | Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy | Ctrough is defined as the plasma concentration at the end of the dosing interval. |
| Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of Idelalisib | Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy | AUC is defined as the plasma concentration at the end of the dosing interval. |
| Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of GS-563117 | Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy | AUC is defined as the plasma concentration at the end of the dosing interval. |
| Levels of Optional Exploratory Biomarkers on Bone Marrow Samples (eg pAKT, pS6 ribosomal protein) and plasma cytokines | Baseline and Day 21 | — |
| Acceptability and Palatability of Idelalisib 10-mg Dispersible Tablet | Day 1 of idelalisib monotherapy and at Day 1, Cycle 1 of idelalisib in combination with RICE chemoimmunotherapy | For participants who cannot swallow a whole tablet, the investigator will ask if the tablet administered as a suspension is palatable and will observe if the participant is able to swallow the dosage form. The acceptability and palatability of idelalisib dispersible tablets administered as an oral suspension (for participants unable to swallow the tablet) will be evaluated by a questionnaire administered to the participant and/or the parent/legal guardian. |
| Pharmacokinetic Parameter: Ctrough of GS-563117 | Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy | Ctrough is defined as the plasma concentration at the end of the dosing interval. |
| Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings | Up to 12 months | — |
| Overall Response Rate (ORR) | Up to 12 months | Overall response rate (ORR) is defined as the proportion of participants who achieve a best response of Complete Response (CR) or Partial Response (PR) after the first dose of idelalisib (either as a result of monotherapy or in combination with RICE chemoimmunotherapy). The screening imaging study will serve as the reference for ORR. |
| Overall Survival (OS) | Up to 5 years | Overall Survival (OS) is defined as the interval from the first dose date of idelalisib to death from any cause. |
Countries
France, Italy, Poland, Spain
Outcome results
None listed