- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03349346
Idelalisib With Rituximab, Ifosfamide, Carboplatin, Etoposide (RICE) in Children and Adolescents
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 Overview
Status
Intervention / Treatment
Study Type
Phase
- Phase 1
Contacts and Locations
Study Locations
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Lille, France, 59000
- Centre Hospitalier Regional Universitaire de Lille
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Genova, Italy, 16147
- Istituto Giannina Gaslini
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Roma, Italy, 00165
- Ospedale Pediatrico Bambino Gesù
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Torino, Italy, 10126
- Infantile Regina Margherita Hospital
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Wrocław, Poland, 50-556
- Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
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Barcelona, Spain, 08035
- Hospital Vall d´hebron
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Madrid, Spain, 28660
- Hospital Universitario HM Monteprincipe
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: 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.
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Tablet (s) or dispersible tablets for suspension administered orally twice daily
Other Names:
375 mg/m^2 administered intravenously
3 mg/m^2 administered intravenously
635 mg/m^2 administered intravenously
100 mg/m^2 administered intravenously
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Experimental: 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.
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Tablet (s) or dispersible tablets for suspension administered orally twice daily
Other Names:
375 mg/m^2 administered intravenously
3 mg/m^2 administered intravenously
635 mg/m^2 administered intravenously
100 mg/m^2 administered intravenously
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Incidence Rate of Dose Limiting Toxicities (DLTs)
Time Frame: Up to Day 21
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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.
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Up to Day 21
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Proportion of Participants Experiencing Adverse Events (AEs)
Time Frame: Up to 12 months
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Up to 12 months
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Proportion of Participants Experiencing Serious Adverse Events (SAEs)
Time Frame: Up to 12 months
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Up to 12 months
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Proportion of Participants Experiencing Adverse Events (AEs) Leading to Idelalisib Interruption, Idelalisib Dose Reduction, Premature Discontinuation of Idelalisib, or Death
Time Frame: Up to 12 months
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Up to 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings
Time Frame: Up to 12 months
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Up to 12 months
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Overall Response Rate (ORR)
Time Frame: Up to 12 months
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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.
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Up to 12 months
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Overall Survival (OS)
Time Frame: Up to 5 years
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Overall Survival (OS) is defined as the interval from the first dose date of idelalisib to death from any cause.
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Up to 5 years
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Progression-Free Survival (PFS)
Time Frame: Up to 12 months
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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.
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Up to 12 months
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Pharmacokinetic Parameter: Cmax of Idelalisib
Time Frame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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Cmax is defined as the maximum observed concentration of drug.
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Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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Pharmacokinetic Parameter: Cmax of GS-563117
Time Frame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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GS-563117 is the metabolite of idelalisib.
Cmax is defined as the maximum observed concentration of drug.
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Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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Pharmacokinetic Parameter: Ctrough of Idelalisib
Time Frame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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Ctrough is defined as the plasma concentration at the end of the dosing interval.
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Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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Pharmacokinetic Parameter: Ctrough of GS-563117
Time Frame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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Ctrough is defined as the plasma concentration at the end of the dosing interval.
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Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of Idelalisib
Time Frame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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AUC is defined as the plasma concentration at the end of the dosing interval.
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Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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Pharmacokinetic Parameter: Area Under the Concentration-Time Curve (AUC) of GS-563117
Time Frame: Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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AUC is defined as the plasma concentration at the end of the dosing interval.
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Predose and up to 24 hours postdose on Day 1 and Cycle 1, Day 5 of idelalisib + RICE combination therapy
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Levels of Optional Exploratory Biomarkers on Bone Marrow Samples (eg pAKT, pS6 ribosomal protein) and plasma cytokines
Time Frame: Baseline and Day 21
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Baseline and Day 21
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Acceptability and Palatability of Idelalisib 10-mg Dispersible Tablet
Time Frame: Day 1 of idelalisib monotherapy and at Day 1, Cycle 1 of idelalisib in combination with RICE chemoimmunotherapy
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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.
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Day 1 of idelalisib monotherapy and at Day 1, Cycle 1 of idelalisib in combination with RICE chemoimmunotherapy
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Lymphoma, Non-Hodgkin
- Lymphoma
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Antineoplastic Agents, Phytogenic
- Topoisomerase II Inhibitors
- Topoisomerase Inhibitors
- Antineoplastic Agents, Immunological
- Carboplatin
- Etoposide
- Ifosfamide
- Rituximab
- Idelalisib
Other Study ID Numbers
- GS-US-313-1090
- 2017-001468-39 (EudraCT Number)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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