Clinical trial NCT03349346: Idelalisib With Rituximab, Ifosfamide, Carboplatin, Etoposide (RICE) in Children and Adolescents
Official title: Phase 1b Trial Evaluating Idelalisib in Children and Adolescents With Relapsed or Refractory Diffuse Large B-cell Lymphoma or Mediastinal B-cell Lymphoma in Combination With RICE
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Diffuse Large B-Cell Lymphoma
Mediastinal B-cell Lymphoma
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2017-11-21
Enrollment: 0
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility 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/ Exclusion criteria may apply.

Primary outcomes:
measure: Incidence Rate of Dose Limiting Toxicities (DLTs)
timeFrame: Up to Day 21
measure: Proportion of Participants Experiencing Adverse Events (AEs)
timeFrame: Up to 12 months
measure: Proportion of Participants Experiencing Serious Adverse Events (SAEs)
timeFrame: Up to 12 months
measure: Proportion of Participants Experiencing Adverse Events (AEs) Leading to Idelalisib Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death
timeFrame: Up to 12 months
Secondary outcomes:
measure: Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings
timeFrame: Up to 12 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 12 months
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 12 months
measure: Pharmacokinetic Parameter: Cmax of Idelalisib
timeFrame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
measure: Pharmacokinetic Parameter: Cmax of GS-563117
timeFrame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
measure: Pharmacokinetic Parameter: Ctrough of Idelalisib
timeFrame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
measure: Pharmacokinetic Parameter: Ctrough of GS-563117
timeFrame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
measure: Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of Idelalisib
timeFrame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
measure: Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of GS-563117
timeFrame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
measure: Levels of Optional Exploratory Biomarkers on Bone Marrow Samples (eg pAKT, pS6 ribosomal protein) and plasma cytokines
timeFrame: Baseline and Day 21
measure: Acceptability and Palatability of Idelalisib 10-mg Dispersible Tablet
timeFrame: Day 1 of idelalisib monotherapy and at Day 1, Cycle 1 of idelalisib in combination with RICE chemoimmunotherapy
Other outcomes:
Locations:
city: Lille
country: France
facility: Centre Hospitalier Régional Universitaire de Lille
city: Genova
country: Italy
facility: Istituto Giannina Gaslini
city: Roma
country: Italy
facility: Ospedale Pediatrico Bambino Gesu
city: Torino
country: Italy
facility: Infantile Regina Margherita Hospital
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu
city: Barcelona
country: Spain
facility: Hospital Vall d´Hebrón
city: Madrid
country: Spain
facility: Hospital Universitario HM Monteprincipe
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: