Idelalisib With Rituximab, Ifosfamide, Carboplatin, Etoposide (RICE) in Children and Adolescents

Diffuse Large B-Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03349346
• Other study ID #: GS-US-313-1090
• Secondary ID: 2017-001468-39
• Status: Withdrawn
• Phase: Phase 1
• Start date: June 2019
• Est. completion date: February 2026

Study information

• Verified date: December 2018
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: February 2026
• Est. primary completion date: February 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 18 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diffuse Large B-Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse
• Mediastinal B-cell Lymphoma

Intervention

Drug:
• Idelalisib
Tablet (s) or dispersible tablets for suspension administered orally twice daily
• Rituximab
375 mg/m^2 administered intravenously
• Ifosfamide
3 mg/m^2 administered intravenously
• Carboplatin
635 mg/m^2 administered intravenously
• Etoposide
100 mg/m^2 administered intravenously

Locations

Country	Name	City	State
France	Centre Hospitalier Régional Universitaire de Lille	Lille
Italy	Istituto Giannina Gaslini	Genova
Italy	Ospedale Pediatrico Bambino Gesu	Roma
Italy	Infantile Regina Margherita Hospital	Torino
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu	Wroclaw
Spain	Hospital Vall d´Hebrón	Barcelona
Spain	Hospital Universitario HM Monteprincipe	Madrid

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

France,  Italy,  Poland,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence Rate of Dose Limiting Toxicities (DLTs)	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.	Up to Day 21
Primary	Proportion of Participants Experiencing Adverse Events (AEs)		Up to 12 months
Primary	Proportion of Participants Experiencing Serious Adverse Events (SAEs)		Up to 12 months
Primary	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	Rate of Grade = 3 Transaminase Elevations Based on Laboratory Findings		Up to 12 months
Secondary	Overall Response Rate (ORR)	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.	Up to 12 months
Secondary	Overall Survival (OS)	Overall Survival (OS) is defined as the interval from the first dose date of idelalisib to death from any cause.	Up to 5 years
Secondary	Progression-Free Survival (PFS)	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.	Up to 12 months
Secondary	Pharmacokinetic Parameter: Cmax of Idelalisib	Cmax is defined as the maximum observed concentration of drug.	Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
Secondary	Pharmacokinetic Parameter: Cmax of GS-563117	GS-563117 is the metabolite of idelalisib. Cmax is defined as the maximum observed concentration of drug.	Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
Secondary	Pharmacokinetic Parameter: Ctrough of Idelalisib	Ctrough is defined as the plasma concentration at the end of the dosing interval.	Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
Secondary	Pharmacokinetic Parameter: Ctrough of GS-563117	Ctrough is defined as the plasma concentration at the end of the dosing interval.	Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
Secondary	Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of Idelalisib	AUC is defined as the plasma concentration at the end of the dosing interval.	Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
Secondary	Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of GS-563117	AUC is defined as the plasma concentration at the end of the dosing interval.	Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
Secondary	Levels of Optional Exploratory Biomarkers on Bone Marrow Samples (eg pAKT, pS6 ribosomal protein) and plasma cytokines		Baseline and Day 21
Secondary	Acceptability and Palatability of Idelalisib 10-mg Dispersible Tablet	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.	Day 1 of idelalisib monotherapy and at Day 1, Cycle 1 of idelalisib in combination with RICE chemoimmunotherapy