Study to Evaluate Nilotinib in Chronic Myelogenous Leukemia (CML) Patients With SubOptimal Response

Phase 4

Completed

• Conditions: Chronic Myelogenous Leukemia in Chronic Phase; Philadelphia Chromosome Positive
• Interventions: Drug: Nilotinib

• Registration Number: NCT01043874
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

To evaluate the major molecular response (MMR) rate at 12 months of nilotinib treatment on study in patients with Philadelphia Chromosome Positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP) who have a suboptimal molecular response to imatinib at 18 months or later.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12
• Study First Submitted: 2010-01-05
• Study First Submitted QC: 2010-01-06
• Study First Posted: 2010-01-07
• Primary Completion: 2013-12
• Study Completion: 2014-01
• Results First Submitted: 2015-01-14
• Results First Submitted QC: 2015-01-22
• Results First Posted: 2015-02-09
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-10
• Last Update Posted: 2016-04-08

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 45

Inclusion Criteria

1. Male or female patients ≥ 18 years of age.

2. ECOG 0, 1, or 2.

3. Have been diagnosed with Ph+ CML-CP and receiving imatinib therapy.

4. Patients with suboptimal molecular response to imatinib treatment continued for at least 18 months (first line therapy)

   Suboptimal molecular response defined as all of the following conditions:

   1. Patients who have achieved CCyR (0% Ph+ chromosomes).
   2. Patients who don't achieve MMR (MMR defined as BCR-ABL/ABL ratio of ≤ 0.1% on the International Scale as detected by RQ-PCR).

   The treatment with imatinib defined as:

   Dose of 300 mg or higher daily must be maintained for a minimum of 3 months prior to study entry.

5. Patients who meet the following laboratory tests criteria:

   1. total bilirubin < 1.5 x ULN,
   2. SGOT and SGPT < 2.5 x ULN,
   3. creatinine < 1.5 x ULN,
   4. Serum amylase and lipase ≤ 1.5 x ULN,
   5. Alkaline phosphatase ≤ 2.5 x ULN unless considered tumor related.
   6. Serum potassium, phosphorus, magnesium and calcium ≥ LLN or correctable with supplements prior to the first dose of study drug.

6. Written informed consent prior to any study related screening procedures being performed.

Exclusion Criteria

1. Prior accelerated phase or blast crisis CML.

2. Previously documented T315I mutations.

3. Presence of chromosomal abnormalities other than Ph+.

4. Previous treatment with any other tyrosine kinase inhibitor except imatinib.

5. Impaired cardiac function including any one of the following:

   1. Complete left bundle branch block
   2. Congenital long QT syndrome or family history of long QT syndrome
   3. History of or presence of significant ventricular or atrial tachyarrhythmias
   4. Clinically significant resting brachycardia (<50 bpm)
   5. QTcF > 450 msec on screening ECG
   6. Use of a ventricular-paced pacemaker
   7. Myocardial infarction during the last 12 months
   8. Other clinically significant heart disease (e.g. congestive heart failure, uncontrolled hypertension, unstable angina).

6. Treatment with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St John's Wort), and the treatment cannot be discontinued or switched to a different medication prior to starting study drug. See Section 6.4.3 for complete list of these medications.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Nilotinib	Nilotinib	400 mg BID

Primary Outcome Measures

Name	Time	Method
MMR Rate at 12 Mos. of Nilotinib Treatment on Study in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Who Have a Suboptimal Molecular Response to Imatinib at 18 Months or Later.	12 months after treatment	MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value

Secondary Outcome Measures

Name	Time	Method
MMR Rate at 24 Months of Nilotinib Treatment on Study in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)	24 months after treatment	MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value
Time to First MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .	month 24	MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value
Duration of MMR of Nilotinib in Patients With Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) .	month 24	MMR is defined as BCR-ABL ratio (%) on IS ≤ 0.1% (corresponds to ≥ 3 log reduction of BCR-ABL transcripts from standardized baseline value

Trial Locations

Locations (1)

Novartis Investigative Site; 🇯🇵 Saga, Japan