Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
Conditions
Keywords
LDE225, nilotinib, Chronic myeloid leukemia, CML, Philadelphia positive, Ph+, resistant, Resistant Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP)
Brief summary
The purpose of this study is to determine the feasibility of administering the combination of nilotinib and LDE225 to patients with chronic or accelerated phase of chronic myeloid leukemia and to establish the maximum tolerated dose (MTD) and/or recommended Phase II dose level (RP2D) of LDE225 in combination with nilotinib.
Interventions
DRUGNilotinib + LDE225
Nilotinib is an aminopyrimidine ATP-competitive inhibitor of the protein tyrosine kinaseactivity of BCR-ABL.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Philadelphia chromosome positive (Ph+) CML in chronic phase (CP) or accelerated phase (AP)with resistance to at least one prior BCR-ABL targeting TKI 2. Documented chronic phase CML 3. Adequate end organ function 4. Female patients of childbearing potential must have a negative serum pregnancy test and must be using highly effective methods of contraception. Male patients with female partners of child-bearing potential must use condoms.
Exclusion criteria
1. Impaired cardiac function 2. Severe and/or uncontrolled concurrent disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol 3. History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis 4. Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to entering the study 5. Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug. 6. Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy | 56 days (2 treatment cycles at 28 days each) | Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC) | 50 days | Assessment of the PK characteristics of nilotinib administered in combination with LDE225 |
| Major molecular response (MMR) rates at 3, 6 and 12 months | 336 days (12 treatment cycles) | Determination of the kinetics of major molecular response |
| No of participants with Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms | 336 days (12 treatment cycles) | Assessment of the safety and tolerability profile of nilotinib in combination with LDE225 |
| Major cytogenic response (MCyR) rates by 3, 6 and 12 months | 336 days (12 treatment cycles) | Determination of major cytogenetic response rates |
| Complete cytogenic response (CCyR) rates by 3, 6 and 12 months | 336 days (12 treatment cycles) | Determination of complete cytogenetic response rates |
| Complete molecular response (CMR) rates at 3, 6 and 12 months | 336 days (12 treatment cycles) | Determination of the kinetics of complete molecular response |
Countries
Canada, France, Germany, Italy, Spain
Outcome results
None listed