Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT01433445 |
Other study ID # |
CLBH589X2106 |
Secondary ID |
2011-000861-10 |
Status |
Completed |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
November 1, 2011 |
Est. completion date |
June 22, 2020 |
Study information
Verified date |
June 2021 |
Source |
Novartis |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
This study will assess safety as well as establish a Recommended Phase II dose of the
combination of panobinostat and ruxolitinib in patients with or without the JAK2V617F
mutation who have been diagnosed with primary myelofibrosis (PMF), Post Essential
Thrombocythemia Myelofibrosis (PET MF), or Post-Polycythemia Vera Myelofibrosis (PPV MF).
Description:
In 2011 the treatment goals for MF focused on symptom-orientated palliation and quality of
life. Both ruxolitinib and panobinostat, as single agents, had shown significant improvement
in both of those treatment goals and ruxolitinib had also shown greater reductions in
splenomegaly compared to the standard of care at that time. To further the benefit seen with
ruxolitinib in MF patients, panobinostat was added to the treatment regimen to act
synergistically in the blockade of the dysregulated pathway driving this disease.
The study was conducted in 2 phases - an escalation phase and an expansion phase.
Escalation phase: the study utilised the Bayesian Logistic Regression Model (BLRM),
incorporating escalation with overdose control (EWOC), which is a well established method for
dose escalation in oncology trials. Following this process, successive cohorts of 3 newly
enrolled patients received increasing doses of ruxolitinib and panobinostat until the maximum
tolerated dose (MTD) or recommended phase II dose (RPIID) was determined. Once the MTD and/or
RPIID were suspected in a minimum of 3 patients, additional patients were enrolled to the
same cohort level to reach a minimum of 9 evaluable patients. The process also included
safety, PK/PD assessments and estimates of efficacy based on measures of splenic reduction at
each dose level.
Expansion: following the determination of the MTD and/or RPIID, a dose expansion phase was
conducted at that dose to further define the safety and tolerability of the combination. At
least 13, and no more than 23, additional patients were to be enrolled into the expansion
phase.