Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations

Phase 4TerminatedNCT01131325

Novartis Pharmaceuticals3 enrolled

Overview

This study is to determine the number of European Leukemia Network (ELN)guideline defined treatment failure events from time of study entry in CML-CP patients with low imatinib trough concentrations treated with nilotinib.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

CML Philadelphia Chromosome Positive (Ph+)Chronic Myelogenous Leukemia Chronic Phase(CML-CP) Patients With Low Imatinib Trough Levels

Interventions

nilotinibDRUG

All patients will receive nilotinib 300mg bid po daily. Nilotinib dose is taken every 12 hours

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Cytogenetically confirmed Ph+ CML-CP Any prior dose of Imatinib * Imatinib 400 mg daily for ≥7 consecutive days prior to imatinib trough collection * Imatinib trough plasma concentration \<850 ng/mL Exclusion Criteria: * Prior documented failure events as defined by ELN guidelines: * Loss of CHR, CCyR, or clonal progression/Ph+ * Less than CHR at 3 months after diagnosis * No CyR at 6 months after diagnosis * Less than PCyR at 12 months after diagnosis * Less than CCyR at 18 months after diagnosis * Prior accelerated phase or blast phase CML * Previously documented T315I mutation * Previous treatment for CML with any other tyrosine kinase inhibitor except for imatinib * Patients who had any other treatment for CML (transplant) except interferon +/- ara- C, imatinib, hydroxyurea and/or anagrelide * Impaired cardiac function * Patients receiving therapy with strong inhibitors of CYP3A4 or medications that prolong the QT interval and cannot be either discontinued or switched to a different medication prior to starting study drug. * Any other malignancy that is clinically significant or requires active intervention. * Major surgery within 4 weeks prior to Day 1 of study or who have not recovered from prior surgery * Treatment with other investigational agents within 30 days of Day 1 * Women who are pregnant, breast feeding, or of childbearing potential without a negative serum test at baseline. Post-menopausal women must be amenorrhoeic for at least 12 months to be considered of non-childbearing potential. Women of childbearing potential must have a negative serum pregnancy test within 7 days of the first dose of nilotinib * Sexually active male and female patients taking nilotinib unwilling to use adequate contraception throughout the trial and 3 months following discontinuation of study drug

Locations (3)

Comprehensive Cancer Centers of Nevada CCC of Nevada (1)

Las Vegas, Nevada, United States

Cancer Center of the High Plains

Amarillo, Texas, United States

Baylor Health Care System/Sammons Cancer Center Dept. of Sammons Cancer (2)

Dallas, Texas, United States

Outcomes

Primary Outcomes

Number of Treatment Failure Events up to 2 Years

Treatment failure events from time of study entry in Complete molecular response-Chronic phase (CML-CP) participants with low imatinib trough concentrations less than 850 nanogram per milliliter (\<850 ng/mL) treated with nilotinib as defined in European LeukemiaNet (ELN)-guideline.

Time frame: up to 2 years

Secondary Outcomes

European LeukemiaNet (ELN)-Defined Optimal Responses

Time frame: up to 2 years

Loss of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR) on Nilotinib

Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as CCyR at 12 cycles if the patient met the CCyR criteria at the Cycle 12 Visit. Major molecular response is defined as values equal or below 0.1% on the International Scale. Complete Molecular Response is defined as a Bcr-Abl (a fusion of gene of Bcr and ABl genes) ratio ≤0.0032% on the International Scale Bcr = breakpoint cluster gene Abl = abelson proto-oncogene.

Time frame: up to 2 years

Duration of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR)Achieved on Nilotinib

Durations of major/complete cytogenetic response is defined as the time from the first documentation of the major/ complete response to the first documentation of the disease progression.

Time frame: up to 2 years

Event-free Survival (EFS), Progression-free Survival (PFS) and Overall Survival (OS) up to 2 Years

Event-free survival was defined as the time from the date of randomization to the date of first occurrence of any of the following events on study treatment: loss of complete hematological response, confirmed loss of complete cytogenetic response (CCyR), confirmed loss of major molecular response (MMR), death from any cause during treatment, progression to the accelerated phase or blast crisis of chronic myelogenous leukemia (CML) per European Leukemia Network (ELN) criteria, whichever was earliest. Progressions free survival is defined as time between Day 1 cycle 1 and time to first documented disease progression or death. Disease progression will be determined as per response criteria. Overall survival time is defined as the time from the treatment start to the date of death due to any reason.

Data from ClinicalTrials.gov

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