* CHDM201K12201
Research type
Research Study
Full title
A phase Ib/II, open label study of siremadlin monotherapy and in combination with donor lymphocyte infusion as a treatment for patients with acute myeloid leukemia post-allogeneic stem cell transplantation who are in complete remission but at high risk for relapse.
IRAS ID
1005152
Contact name
Cecilia Laudisa Verderamo
Contact email
Sponsor organisation
Novartis Pharma AG
Eudract number
2021-003596-34
Clinicaltrials.gov Identifier
Research summary
Summary of Research:
This is a study of siremadlin treatment only (a medicine) or siremadlin in combination with donor lymphocyte (a type of immune cell) infusion in acute myeloid leukaemia's disease patients who previously have had a transplant with stem cell (very early cells made in the bone marrow) from a donor and there is a complete response to treatment, but they have high risk of the disease returning. This study aims to confirm the dose of siremadlin that has the best results, is safe and tolerated by patients.
Up to 42 adult patients at 18 hospital sites around the world will be given the opportunity to join the study to evaluate up to 3 different doses of Siremadlin, in order to select a dose that is considered safe and tolerated.
Every participant will follow a different treatment strategy, which contains three consecutive phases for a maximum of 24 cycles in total (each cycle = 28 days, or 42 days for the 3 cycles of combination phase).
Priming phase
After an initial screening period of up to 28 days, eligible patients will take Siremadlin for at least 2 cycles (each cycle = 28 days). After these 2 cycles, patients that are not eligible to have donor lymphocyte infusion may continue in this phase taking only Siremadlin. During this phase, patients will have regular visits to the hospital site during days 1, 2 and 5 for the first cycle; days 1 and 2 for the second cycle; and then every 28 days for subsequent cycles.
Combination Phase
After these 2 cycles of Siremadlin, patients that are eligible to have donor lymphocyte infusion will continue taking Siremadlin in combination with donor lymphocyte infusion (up to a total of 3 combination cycles (each combination cycle = 42 days).
During this phase, patients will have regular visits to the hospital site during days 1, 3 and 5 for each of the 3 cycles.
Maintenance phase
Patients, who have completed the combination phase, will take only Siremadlin again.Research Summary:
The first dose escalation meeting was held on 18-Sep-2023 for Cohort 1 at siremadlin monotherapy 30 mg QD Days 1-5 of a 28-day cycle, where no new safety concerns were identified;, it was recommended to treat additional participants with siremadlin monotherapy. However, Novartis decided to permanently halt the recruitment of new participants into study CHDM201K12201 in Sep-2023 (recruitment halt letter dated 21-Sep-2023 was sent to investigators on 25-Sep-2023). As a result, recruitment in Part 1 was permanently halted after the Cohort 1 dose escalation meeting, and Part 2 of the study was not opened. This decision was not based on any safety findings or safety concerns with siremadlin but rather on a Novartis strategic consideration. The decision about the permanent recruitment halt was documented in the early termination plan for the study. The study data was analyzed and reported based on all available data up to the data cut-off 26-Oct-2023 of this final CSR.At the time of termination decision, 9 participants were screened among 6 investigational centers, and 8 participants received siremadlin monotherapy 30 mg QD
REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
22/NE/0142
Date of REC Opinion
6 Jun 2022
REC opinion
Further Information Favourable Opinion