Nilotinib and LDE225 in the Treatment of Chronic or Accelerated Phase Myeloid Leukemia in Patients Who Developed Resistance to Prior Therapy

Phase 1

Completed

• Conditions: Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
• Interventions: Drug: Nilotinib + LDE225

• Registration Number: NCT01456676
• Lead Sponsor: Novartis Pharmaceuticals

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-10-14
• Study First Submitted QC: 2011-10-20
• Study First Posted: 2011-10-21
• Study Start: 2012-01
• Primary Completion: 2014-02
• Study Completion: 2014-02
• Status Verified: 2016-09
• Last Update Submitted: 2020-12-06
• Last Update Posted: 2020-12-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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/exclusion criteria may apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nilotinib + LDE225	Nilotinib + LDE225	The planned dose of nilotinib 400 mg b.i.d (twice a day) was selected for the combination as this is the dose approved for the treatment of the patient population that will be included in the present study. The starting dose for LDE225 chosen for the current study is 400 mg once daily(q.d.). The maximum dose of LDE225 that will be tested in combination with nilotinib is 800 mg once dail.y

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Complete molecular response (CMR) rates at 3, 6 and 12 months	336 days (12 treatment cycles)	Determination of the kinetics of complete molecular response
Major cytogenic response (MCyR) rates by 3, 6 and 12 months	336 days (12 treatment cycles)	Determination of major cytogenetic response rates
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
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
Complete cytogenic response (CCyR) rates by 3, 6 and 12 months	336 days (12 treatment cycles)	Determination of complete cytogenetic response rates

Trial Locations

Locations (1)

Novartis Investigative Site; 🇪🇸 Madrid, Spain