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

Gilead Sciences

Status and phase: Withdrawn; Phase 1

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

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT03349346

GS-US-313-1090

2017-001468-39 (EudraCT Number)

Details and patient eligibility

About

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)

Sex: All

Ages: 1 to 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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0 participants in 2 patient groups

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

Experimental group

Description:

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.

Treatment:

Drug: Etoposide

Drug: Idelalisib

Drug: Rituximab

Drug: Carboplatin

Drug: Ifosfamide

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

Experimental group

Description:

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.

Treatment:

Drug: Etoposide

Drug: Idelalisib

Drug: Rituximab

Drug: Carboplatin

Drug: Ifosfamide