The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D), safety and toxicity, and pharmacokinetics (PK) of ixazomib administered intravenously in combination with multiagent reinduction chemotherapy in pediatric participants with relapsed/refractory ALL or LLy.
29-Apr-2020 Enrollment of new patients into this study has been paused due to the COVID-19 situation. The duration of this pause is dependent on the leveling and control of the COVID-19 pandemic. The drug being tested in this study is called Ixazomib. Ixazomib is being tested to determine the MTD or RP2D of intravenous ixazomib when administered in combination with multiagent chemotherapy (reinduction therapy) in pediatric participants with relapsed or refractory ALL or relapsed/refractory LLy. The study will enroll approximately 18 participants. Doses of ixazomib will be escalated according to a standard 3+3 dose escalation schema. Participants aged \>= 1 year will receive the starting dose of 1.0 mg/m\^2 and participants aged \<1 year will receive the starting dose of 0.03 mg/kg. Ixazomib will be administered in combination with multiagent reinduction therapy. The dose escalation phase will determine the MTD and/or RP2D of ixazomib. Dose escalation will be based on the observed safety and tolerability data. Participants aged \<1 year will be assessed separately and will not contribute to the dose escalation assessment. This multi-center trial will be conducted in the United States and Spain. The overall time to participate in this study is approximately 30 months. Participants will be followed up to Day 60 after the first dose of study drug for a follow-up assessment.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Ixazomib intravenous injection in combination with reduction chemotherapy.
University of Mississippi Medical Center
Jackson, Mississippi, United States
Washington University School of Medicine
St Louis, Missouri, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
St Jude Children's Research Hospital
Memphis, Tennessee, United States
Number of Participants with Dose-limiting Toxicities (DLT) During Reinduction Chemotherapy
DLT: Grade 4 nonhematologic toxicity after first dose of ixazomib and is probably/definitely attributable to the ixazomib treatment regimen, with exceptions, example fever/infection with/without hospitalization, fatigue and gastrointestinal symptoms, hypofibrinogenemia, metabolic/laboratory abnormalities that resolve to less than or equal to(\<=)Grade 2 within 7 days. Any Grade 3/4 nonhematologic toxicity after first dose of ixazomib that is possibly/probably/definitely attributable to the ixazomib treatment regimen and results in omission of subsequent dose of chemotherapy, with exception of fever/infection. Hematologic toxicities: Failure to recover a peripheral absolute neutrophil count (ANC) ≥0.5\*10\^9 per liter (/L) and a platelet count ≥50\*10\^9/L due to documented bone marrow hypoplasia (cellularity \<10 20%) within 42 days after the beginning of systemic chemotherapy without evidence of active disease by bone marrow evaluation or active infection.
Time frame: Up to Day 29
Number of Participants With Grade 3 or Higher Treatment Emergent Adverse Events (TEAEs) Based on Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0
Time frame: Up to 30 months
Number of Participants With Worst Shift From Baseline Values to Post-baseline Values in Clinical Laboratory Parameters
Time frame: Up to 30 months
AUCt: Area Under the Plasma Concentration-time Curve From Time 0 to Time t for Ixazomib
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose and Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose
Cmax: Maximum Observed Plasma Concentration for Ixazomib
Time frame: Day 1 pre-dose and at multiple time points (up to 72 hours) post-dose and Day 11 pre-dose and at multiple time points (up to 264 hours) post-dose
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Hospital Universitario Vall d'Hebron - PPDS
Barcelona, Spain
C.H. Regional Reina Sofia
Córdoba, Spain
Hospital Universitario La Paz
Madrid, Spain
Overall Response Rate (ORR)
ORR is defined as the percentage of participants with complete response (CR) or CR with incomplete platelet recovery (CRp) based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR is defined as bone marrow with less than 5 percent (%) blast by morphology, no evidence of circulating blasts or extramedullary disease, and recovery of peripheral counts (ANC \>=1.0\*10\^9/L and a platelet count \>=100\*10\^9/L). CRp is defined as bone marrow with \<5% blasts by morphology, no evidence of circulating blasts or extramedullary disease, and recovery of ANC (\>1000/mcL) but insufficient recovery of platelets (counts \<100, 000/mcL).
Time frame: Up to 30 months