Intravenous Ixazomib in Pediatric Participants With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LLy)
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|ClinicalTrials.gov Identifier: NCT03888534|
Recruitment Status : Not yet recruiting
First Posted : March 25, 2019
Last Update Posted : June 9, 2020
|Condition or disease||Intervention/treatment||Phase|
|Precursor Cell Lymphoblastic Leukemia-lymphoma||Drug: Ixazomib||Phase 1|
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 (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||Open-Label Phase 1 Study to Assess the Maximum Tolerated Dose, Pharmacokinetics, and Safety of Ixazomib Administered Intravenously to Pediatric Patients Aged 0 to <18 Years With Relapsed or Refractory Acute Lymphoblastic Leukemia, With or Without Extramedullary Disease, or Relapsed or Refractory Lymphoblastic Lymphoma|
|Estimated Study Start Date :||August 31, 2020|
|Estimated Primary Completion Date :||August 30, 2022|
|Estimated Study Completion Date :||August 30, 2022|
Ixazomib, injection, intravenously, once on Days 1, 4, 8, and 11 in a single 29-day treatment cycle in combination with multiagent reinduction therapy. Participants >= 1 year will receive the starting dose of 1.0 milligram per square meter (mg/m^2) and <1 year will receive the starting dose of 0.03 milligram per kilogram (mg/kg). The dose escalation phase will determine the MTD or RP2D of Ixazomib. Dose of Ixazomib will be escalated based on the observed safety and tolerability data.
Ixazomib intravenous injection in combination with reduction chemotherapy.
Other Name: MLN9708
- Number of Participants with Dose-limiting Toxicities (DLT) During Reinduction Chemotherapy [ Time Frame: Up to Day 29 ]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.
- 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 ]
- Overall Response Rate (ORR) [ Time Frame: Up to 30 months ]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).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03888534
|Contact: Takeda Study Registration Call Centeremail@example.com|
|United States, Mississippi|
|University of Mississippi Medical Center|
|Jackson, Mississippi, United States, 39216|
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|United States, Tennessee|
|St Jude Children's Research Hospital|
|Memphis, Tennessee, United States, 38105|
|Hospital Universitario Vall d'Hebron - PPDS|
|Barcelona, Spain, 8035|
|C.H. Regional Reina Sofia|
|Cordoba, Spain, 14004|
|Hospital Universitario La Paz|
|Madrid, Spain, 28046|
|Study Director:||Medical Director||Millennium Pharmaceuticals, Inc.|