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

CML Clinical Trial

— MACS1148  

Official title:

A Multi-center, Single Arm Study of Nilotinib in Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Patients With Low Imatinib Trough Plasma Concentrations

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01131325
• Other study ID #: CAMN107AUS20
• Status: Terminated
• Phase: Phase 4
• Start date: October 21, 2010
• Est. completion date: May 12, 2011

Study information

• Verified date: October 2020
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: May 12, 2011
• Est. primary completion date: May 12, 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

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

Locations

Country	Name	City	State
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	Comprehensive Cancer Centers of Nevada CCC of Nevada (1)	Las Vegas	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	up to 2 years
Secondary	European LeukemiaNet (ELN)-Defined Optimal Responses		up to 2 years
Secondary	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.	up to 2 years
Secondary	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.	up to 2 years
Secondary	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.	up to 2 years
Secondary	European LeukemiaNet (ELN)-Defined Suboptimal Events		up to 2 years
Secondary	Number of Participants Reported Adverse Events	An AE is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, or is an event of possible drug-induced liver injury.	Up to 2 years