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

NCT03349346 | Withdrawn Phase 1 FDA Drug

• 2 other identifiers: GS-US-313-10902017-001468-39
• Study Type: interventional
• Target: N/A
• Locations: 4 countries
• Sites: 7

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)

Conditions

Diffuse Large B-Cell Lymphoma; Mediastinal B-cell Lymphoma

Outcome Measures

Primary Outcomes (4)

• 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

• 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 Outcomes (12)

• Rate of Grade ≥ 3 Transaminase Elevations Based on Laboratory Findings

  Up to 12 months

• Overall Response Rate (ORR)

  Up to 12 months

• Overall Survival (OS)

  Up to 5 years

• Progression-Free Survival (PFS)

  Up to 12 months

• 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

Study Arms (2)

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

EXPERIMENTAL

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.

Drug: Idelalisib; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide

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

EXPERIMENTAL

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.

Drug: Idelalisib; Drug: Rituximab; Drug: Ifosfamide; Drug: Carboplatin; Drug: Etoposide

Interventions

Idelalisib DRUG

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

Also known as: Zydelig®

Cohort 1- Participants 12 to less than 18 years of age; Cohort 2- Participants 1 to less than 12 years of age

Rituximab DRUG

375 mg/m\^2 administered intravenously

Cohort 1- Participants 12 to less than 18 years of age; Cohort 2- Participants 1 to less than 12 years of age

Ifosfamide DRUG

3 mg/m\^2 administered intravenously

Cohort 1- Participants 12 to less than 18 years of age; Cohort 2- Participants 1 to less than 12 years of age

Carboplatin DRUG

635 mg/m\^2 administered intravenously

Cohort 1- Participants 12 to less than 18 years of age; Cohort 2- Participants 1 to less than 12 years of age

Etoposide DRUG

100 mg/m\^2 administered intravenously

Cohort 1- Participants 12 to less than 18 years of age; Cohort 2- Participants 1 to less than 12 years of age

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (7)

Centre Hospitalier Régional Universitaire de Lille

Lille, 59000, France

Location

Istituto Giannina Gaslini

Genova, 16147, Italy

Location

Ospedale Pediatrico Bambino Gesu

Roma, 00165, Italy

Location

Infantile Regina Margherita Hospital

Torino, 10126, Italy

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu

Wroclaw, 50-556, Poland

Location

Hospital Vall d´Hebrón

Barcelona, 08035, Spain

Location

Hospital Universitario HM Monteprincipe

Madrid, 28660, Spain

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

idelalisib; Rituximab; Ifosfamide; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2017
• First Posted: November 21, 2017
• Study Start: June 1, 2019
• Primary Completion: February 1, 2021
• Study Completion: February 1, 2026
• Last Updated: December 11, 2018

Record last verified: 2018-12

Locations

FR (1); IT (3); ES (2); PL (1)