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

NCT ID: NCT03349346

Last Updated: 2018-12-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-30

Study Completion Date

2026-02-28

Brief Summary

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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)

Detailed Description

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Conditions

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Diffuse Large B-Cell Lymphoma Mediastinal B-cell Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1- Participants 12 to less than 18 years of age

Participants will receive idelalisib monotherapy (from day 1 to day 21), followed by combination therapy with RICE. Upon enrollment, participants will be assigned to one of the 3 dose levels during idelalisib monotherapy (Dose level 1 = 55 mg/m\^2 twice daily (BID), Dose level 2 = 85 mg/m\^2 BID, Dose level 3 = 125 mg/m\^2 BID) administered as 50 mg, 100 mg or 150 mg tablets as appropriate, or as 10 mg dispersible tablets for oral suspension for participants who cannot swallow tablets.

* Day 1: single dose of idelalisib
* Day 2 up to Day 21: initiate and continue idelalisib BID dosing
* Day 22 for up to 12 months: idelalisib twice per day in combination with RICE. Cycles of RICE will be administered over 5 days every 3 weeks (Day 1: rituximab; Day 3: rituximab, ifosfamide, carboplatin, etoposide; Days 4 and 5: ifosfamide, etoposide) starting day 22 (or earlier if there is evidence of clinical progression while on idelalisib monotherapy) for up to 12 months.

Group Type EXPERIMENTAL

Idelalisib

Intervention Type DRUG

Tablet (s) or dispersible tablets for suspension administered orally twice daily

Rituximab

Intervention Type DRUG

375 mg/m\^2 administered intravenously

Ifosfamide

Intervention Type DRUG

3 mg/m\^2 administered intravenously

Carboplatin

Intervention Type DRUG

635 mg/m\^2 administered intravenously

Etoposide

Intervention Type DRUG

100 mg/m\^2 administered intravenously

Cohort 2- Participants 1 to less than 12 years of age

Participants will receive one of the 3 doses of idelalisib monotherapy (from day 1 to day 21) followed by combination therapy with RICE. Idelalisib will be administered as as 50 mg, 100 mg or 150 mg tablets as appropriate, or as 10 mg dispersible tablets for oral suspension for participants who cannot swallow tablets. Participants will will be enrolled at dose level 1 once tolerability is demonstrated in the older cohort (Cohort 1). Thereafter, both age cohorts will be dose escalated independently.

* Day 1: single dose of idelalisib
* Day 2 up to Day 21: initiate and continue idelalisib BID
* Day 22 for up to 12 months: idelalisib twice per day in combination with RICE. Cycles of RICE will be administered over 5 days every 3 weeks (Day 1: rituximab; Day 3: rituximab, ifosfamide, carboplatin, etoposide; Days 4 and 5: ifosfamide, etoposide) starting day 22 (or earlier if there is evidence of clinical progression while on idelalisib monotherapy) for up to 12 months.

Group Type EXPERIMENTAL

Idelalisib

Intervention Type DRUG

Tablet (s) or dispersible tablets for suspension administered orally twice daily

Rituximab

Intervention Type DRUG

375 mg/m\^2 administered intravenously

Ifosfamide

Intervention Type DRUG

3 mg/m\^2 administered intravenously

Carboplatin

Intervention Type DRUG

635 mg/m\^2 administered intravenously

Etoposide

Intervention Type DRUG

100 mg/m\^2 administered intravenously

Interventions

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Idelalisib

Tablet (s) or dispersible tablets for suspension administered orally twice daily

Intervention Type DRUG

Rituximab

375 mg/m\^2 administered intravenously

Intervention Type DRUG

Ifosfamide

3 mg/m\^2 administered intravenously

Intervention Type DRUG

Carboplatin

635 mg/m\^2 administered intravenously

Intervention Type DRUG

Etoposide

100 mg/m\^2 administered intravenously

Intervention Type DRUG

Other Intervention Names

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Zydelig®

Eligibility Criteria

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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

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
Minimum Eligible Age

1 Year

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Centre Hospitalier Régional Universitaire de Lille

Lille, , France

Site Status

Istituto Giannina Gaslini

Genova, , Italy

Site Status

Ospedale Pediatrico Bambino Gesu

Roma, , Italy

Site Status

Infantile Regina Margherita Hospital

Torino, , Italy

Site Status

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroclaw, , Poland

Site Status

Hospital Vall d´Hebrón

Barcelona, , Spain

Site Status

Hospital Universitario HM Monteprincipe

Madrid, , Spain

Site Status

Countries

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France Italy Poland Spain

Other Identifiers

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2017-001468-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-313-1090

Identifier Type: -

Identifier Source: org_study_id