Phase I/II Idasanutlin in combination for pediatric/young adults
Research type
Research Study
Full title
A PHASE I/II, MULTICENTER, OPEN-LABEL, MULTI-ARM STUDY EVALUATING THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PRELIMINARY ACTIVITY OF IDASANUTLIN IN COMBINATION WITH EITHER CHEMOTHERAPY OR VENETOCLAX IN THE TREATMENT OF PEDIATRIC AND YOUNG ADULT PATIENTS WITH RELAPSED/REFRACTORY ACUTE LEUKEMIAS OR SOLID TUMORS
IRAS ID
264068
Contact name
Lynley Marshall
Contact email
Sponsor organisation
F. Hoffmann-La Roche Ltd
Eudract number
2018-004579-11
Clinicaltrials.gov Identifier
117005, IND
Duration of Study in the UK
5 years, 0 months, days
Research summary
Acute myeloid leukaemia (AML) is a rare childhood cancer, occuring in approximately 7 children per million annually, but AML remains a significant cause of childhood cancer mortality. Idasanutlin has been shown to block tumour development. Venetoclax is a medication that is currently approved for use in adult chronic lymphocytic leukaemia. This study will determine the best dose of idasanutlin for children and young adults (either as a single medication or in combination with venetoclax or chemotherapy), and to assess the effects, good or bad, of idasanutlin and either venetoclax or chemotherapy in patients with acute leukaemia’s or solid tumours.
The study is divided into three parts. Part 1 will establish the dose used for the study and will only enrol patients less than 18 years old. Part 2 evaluates the safety of idasanutlin in combination with chemotherapy or venetoclax in newly enrolled patients and Part 3 will gather further data on idasanutlin combination groups. Both Part 2 and 3 will enrol patients with neuroblastoma or acute leukaemia’s aged from birth to 30 years old.
During this study, participants will have about 6 visits for the first cycle, 4 visits for the second cycle and 2 visits for each subsequent cycle. Each cycle lasts about 28 days and study medication will be administered for the first 5 days orally for each cycle. Visits may last 2-8 hours. The total length of the study is expected to be approximately 5 years.
Approximately 93-126 patients will be enrolled in the Study Parts 1 and 2. After completion of the initial response assessment, an additional 20-30 patients may be enrolled for a combination regimen in each tumour type, up to approximately 220 patients.
Participants will have multiple study visits including study assessments, these include physical exams and radiological procedures.
Lay summary of study results: In Part 1a of the study, the highest dose of idasanutlin given on its own that was considered not to have unacceptable unwanted effects in paediatric patients with r/r solid tumours was 4.5 mg/kg given orally on days 1-5 of a 28-day cycle.In the Part 1b of the study, the combinations of idasanutlin with venetoclax and idasanutlin with chemotherapy (cyclophosphamide and topotecan) were not considered sufficiently tolerable at the evaluated dose levels in patients with neuroblastoma.
The most common unwanted effects for both idasanutlin given on its own and given in combination with chemotherapy or venetoclax that prevented higher doses being given were effects on the blood cells, particularly low levels of cells that help fight infection (neutrophils) and cells that help the blood clot (platelets).
Limited responses were observed in the study for either idasanutlin given on its own or in combination with venetoclax or chemotherapy.
Increasing doses of idasanutlin yielded generally higher levels in the blood, though there was significant variability among patients, as has been observed in adults in other studies.The limited efficacy and the safety results led to the decision to close the neuroblastoma cohorts in Part 1b and the study overall
REC name
South Central - Hampshire A Research Ethics Committee
REC reference
20/SC/0007
Date of REC Opinion
21 Jan 2020
REC opinion
Favourable Opinion