Phase 1b Study of Blinatumomab with AMG 404 for Adults with ALL
Research type
Research Study
Full title
A Phase 1b Open-label Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Administration of Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (ALL)
IRAS ID
278816
Contact name
Adele Fielding
Contact email
Sponsor organisation
Amgen
Eudract number
2019-004304-36
Duration of Study in the UK
3 years, 0 months, 4 days
Research summary
Historically, treatment options for adults with Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (R/R B-ALL) have been limited to conventional cytotoxic chemotherapies. These common treatment regimens to treat adult patients with R/R B-ALL have limited effectiveness and their long term outlook remains poor. There is no standard approach to care for this population.
Blinatumomab is now an option since its approval to treat adults with relapsed/refractory ALL in 2014 by the Food and Drug Administration (FDA) and by the European Medicines Agency in 2015. Current evidence demonstrates clinical response of R/R B-ALL patients treated with intravenous (IV) Blinatumomab have longer Overall survival and better remission rates in 12 weeks , compared to standard of care and chemotherapy group respectively.
AMG 404, another investigational product being used in this study, is produced for its biological mechanism involving Enhancement of anti-tumor immunity. AMG 404 is currently being tested in Amgen-sponsored Studies. To date, evidence shown the compound has been well-tolerated as well as similar safety profile and effect compared to other similar approved agent.
The study will see if blinatumomab in combination with AMG 404 causes any side effects. It will also look at what doses of AMG 404 when combined with blinatumomab are safe for people to take.
Participants on this study will receive blinatumomab and AMG 404 for at least 2 cycles/treatment and up to 5 cycles /treatment Each cycle will be 42 days in total, which includes 28 days of blinatumomab continuous intravenous (IV) infusion, followed by a 14-day treatment-free interval. AMG 404 will be given as a short 30 minute intravenous infusion every 4 weeks, starting on day 11 of the first cycle of blinatumomab.
Hospitalisation for the first 12 days in cycle 1, and 3 days at the start of cycle 2 and intensive sampling is required.
The first part of the study focuses on the determination of the maximum tolerated/tested dose. 3 Cohorts of 3-6 participants will be tested for a specific dose. Participants Response and safety will be closely monitored to determine the does and continuation or discontinuation of the study.The second part of study is for an expanded cohort of up to 15 evaluable participants based on the maxima benefit does determined in first part of study.Participants Response and safety will be closely monitored for safety and response so to ensure participants are benefit from the treatment or discontinuation of the study.LAY SUMMARY OF STUDY RESULTS:
What Were the Overall Results of the Study?
One of the main reasons for doing this study was to see which doses of the combination of blinatumomab and AMG 404 were safe for people to take. The study doctors checked to see if there were any ‘dose-limiting toxicity’ side-effects experienced by the participants during study treatment and it was determined that both the combination of blinatumomab and 240 mg of AMG 404 and the combination of blinatumomab and 480 mg of AMG 404 were safe and tolerated by the participants, with no dose-limiting toxicity side-effects reported.
The study was stopped earlier than planned (not as many participants were included as planned) because there was no clear benefit of the combined treatment of blinatumomab and AMG 404. The study was not stopped due to safety reasons.
https://www.clinicaltrials.gov/study/NCT04524455?term=NCT04524455&rank=1&tab=resultsREC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
20/WM/0201
Date of REC Opinion
17 Sep 2020
REC opinion
Further Information Favourable Opinion