MACS1148: Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01131325
• Collaborator: (none)
• Enrollment: 3
• Locations: 3
• Arm: 1
• Actual Duration (Months): 6.7
• Patient Per Site: 1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
CML; Philadelphia Chromosome Positive (Ph+); Chronic Myelogenous Leukemia Chronic Phase(CML-CP) Patients With Low Imatinib Trough Levels	Drug: nilotinib	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Oct 21, 2010
• Actual Primary Completion Date: May 12, 2011
• Actual Study Completion Date: May 12, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nilotinib	Drug: nilotinib; All patients will receive nilotinib 300mg bid po daily. Nilotinib dose is taken every 12 hours; Other Names: AMN107 Tasigna

Outcome Measures

Primary Outcome Measures

1. Number of Treatment Failure Events up to 2 Years [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.

Secondary Outcome Measures

1. European LeukemiaNet (ELN)-Defined Optimal Responses [up to 2 years]

2. Loss of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR) on Nilotinib [up to 2 years]

   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.

3. Duration of Complete Cytogenetic Response (CCyR), Major Molecular Response (MMR) and Complete Molecular Response (CMR)Achieved on Nilotinib [up to 2 years]

   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.

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

5. European LeukemiaNet (ELN)-Defined Suboptimal Events [up to 2 years]

6. Number of Participants Reported Adverse Events [Up to 2 years]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Cancer Centers of Nevada CCC of Nevada (1)	Las Vegas	Nevada	United States	89109
2	Cancer Center of the High Plains	Amarillo	Texas	United States	79106
3	Baylor Health Care System/Sammons Cancer Center Dept. of Sammons Cancer (2)	Dallas	Texas	United States	75246

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01131325
• Other Study ID Numbers: CAMN107AUS20
• First Posted: May 26, 2010
• Last Update Posted: May 20, 2021
• Last Verified: Oct 1, 2020

• Keywords provided by Novartis Pharmaceuticals: Philadelphia chromosome positive; Ph+; chronic myelogenous leukemia chronic phase; CML-CP; low imatinib trough levels
• Additional relevant MeSH terms: Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome

Study Results

Participant Flow

Recruitment Details	The study was conducted at 3 centers in the United States.
Pre-assignment Detail	A total of 3 participants were enrolled in the study, of which 1 discontinued the study due to Adverse Event (AE) and 2 participants discontinued as the study got terminated.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received nilotinib 300 milligram (mg) twice daily (bid) through the mouth (po), every 12 hours in a continuous 28-day cycle up to 2 years.
Period Title: Overall Study
STARTED	3
COMPLETED	0
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
Overall Participants	3
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	3 100%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	3 100%

Outcome Measures

1. Primary Outcome

Title	Number of Treatment Failure Events up to 2 Years
Description	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

Outcome Measure Data

Analysis Population Description

The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
Measure Participants	0

2. Secondary Outcome

Title	European LeukemiaNet (ELN)-Defined Optimal Responses
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
Measure Participants	0

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
Measure Participants	0

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
Measure Participants	0

5. Secondary Outcome

Title	Event-free Survival (EFS), Progression-free Survival (PFS) and Overall Survival (OS) up to 2 Years
Description	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.
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
Measure Participants	0

6. Secondary Outcome

Title	European LeukemiaNet (ELN)-Defined Suboptimal Events
Time Frame	up to 2 years

Outcome Measure Data

Analysis Population Description

The overall number of participants considered for analysis was "0" due to the premature termination of the study and low enrollment; The efficacy and quality of life assessments were not collected and reported in the study.

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
Measure Participants	0

7. Secondary Outcome

Title	Number of Participants Reported Adverse Events
Description	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.
Time Frame	Up to 2 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Nilotinib
Arm/Group Description	Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
Measure Participants	3
Count of Participants [Participants]	2 66.7%

Adverse Events

Time Frame	up to 2 years
Adverse Event Reporting Description	Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical examination or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Arm/Group Title	Nilotinib
Arm/Group Description	Participants received nilotinib 300 mg, BID po, every 12 hours in continuous 28-day cycle up to 2 years.
All Cause Mortality
	Nilotinib
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Serious Adverse Events
	Nilotinib
	Affected / at Risk (%)	# Events
Total	0/3 (0%)
Other (Not Including Serious) Adverse Events
	Nilotinib
	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)
Blood and lymphatic system disorders
Thrombocytopenia	1/3 (33.3%)
Neutropenia	1/3 (33.3%)
Gastrointestinal disorders
Nausea	1/3 (33.3%)
Vomiting	1/3 (33.3%)
General disorders
Fatigue	1/3 (33.3%)
Mild sweats	1/3 (33.3%)
Infections and infestations
Sore Throat	1/3 (33.3%)
Musculoskeletal and connective tissue disorders
Muscle cramps - legs	1/3 (33.3%)
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic	1/3 (33.3%)
Skin and subcutaneous tissue disorders
Rash	1/3 (33.3%)
Pruritus Genital	1/3 (33.3%)

Limitations/Caveats

The study was terminated early due to slow enrollment.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.