Trial Outcomes & Findings for Study of Nilotinib as First Line Treatment in Philadelphia Chromosome Positive(Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) (NCT NCT01274351)

Last Updated: 2020-09-01

Results Overview

Major Molecular Response (MMR) was defined as BCR-ABL1\^IS ≤0.1%, on the International Scale \[BCR-ABL1IS\]) by 12 months. BCR is the Breakpoint Cluster Region gene / BCR gene product and ABL is the Abelson proto-oncogene. BCR-ABL is the Fusion gene from BCR and ABL/Protein product from BCR-ABL. Participants who withdrew prematurely or those who failed to provide data for the study for other reasons were designated as premature withdrawal or inevaluable, respectively, and were included in the ITT analysis as non-responders.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

112 participants

Primary outcome timeframe

12 months

Results posted on

2020-09-01

Participant Flow

A total of 112 participants were enrolled into the study from the 15 sites in Turkey.

This was an open-label study with one treatment arm. The study did not involve a reference treatment.

Participant milestones

Participant milestones
Measure	Nilotinib administered orally at a dose of 300 mg twice daily for 24 months
Overall Study STARTED	112
Overall Study COMPLETED	92
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Nilotinib administered orally at a dose of 300 mg twice daily for 24 months
Overall Study Lost to Follow-up	1
Overall Study patient not compliant with the protocol	1
Overall Study Pregnancy	1
Overall Study Death	2
Overall Study Withdrawal by Subject	3
Overall Study Adverse Event	8
Overall Study progression of disease	3
Overall Study hospitalization	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nilotinib n=112 Participants administered orally at a dose of 300 mg twice daily for 24 months
Age, Continuous	47 years n=112 Participants
Sex: Female, Male Female	49 Participants n=112 Participants
Sex: Female, Male Male	63 Participants n=112 Participants

PRIMARY outcome

Timeframe: 12 months

Population: Intent-to-treat (ITT) analysis set

Outcome measures

Outcome measures
Measure	Nilotinib n=112 Participants administered orally at a dose of 300 mg twice daily for 24 months
Percentage of Participants Who Achieved Major Molecular Response (MMR) During the First 12 Months	74 Participants

SECONDARY outcome

Timeframe: 3, 6, 9, 15, 18, 21 and 24 months

Population: ITT analysis set

Outcome measures

Outcome measures
Measure	Nilotinib n=112 Participants administered orally at a dose of 300 mg twice daily for 24 months
Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months 3 months	28 Participants
Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months 6 months	57 Participants
Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months 9 months	67 Participants
Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months 15 months	84 Participants
Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months 18 months	92 Participants
Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months 21 months	93 Participants
Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months 24 months	93 Participants

SECONDARY outcome

Timeframe: Month 6 and 12

Population: ITT analysis set included only the participants who had measurements i.e. excluding drop outs.

CCyR rate is identified as the rate of patients who had 0% of Ph+ metaphase.

Outcome measures

Outcome measures
Measure	Nilotinib n=112 Participants administered orally at a dose of 300 mg twice daily for 24 months
Percentage of Participants With Complete Cytogenetic Response (CCyR) at Month 6 and 12 Month 6	89 Participants
Percentage of Participants With Complete Cytogenetic Response (CCyR) at Month 6 and 12 Month 12	84 Participants

SECONDARY outcome

Timeframe: Month 3, 6, 9, 12, 18 and 24

Population: ITT analysis set included only the participants who had measurements i.e. excluding drop outs.

A confirmed complete hematological response (CHR) is defined when all of the following criteria are achieved: WBC \<10 x 109/L, thrombocyte \<450 x 109/L, myelocyte + metamyelocyte \<%5 in blood, no sign of blast and promyelocyte in blood, basophil \<%5, and no sign of extramedullary involvement.

Outcome measures

Outcome measures
Measure	Nilotinib n=112 Participants administered orally at a dose of 300 mg twice daily for 24 months
Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24 Month 3	104 Participants
Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24 Month 6	102 Participants
Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24 Month 9	100 Participants
Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24 Month 12	96 Participants
Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24 Month 18	93 Participants
Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24 Month 24	92 Participants

SECONDARY outcome

Timeframe: 24 months

Population: ITT analysis set. Only participants with a MMR were included in the analysis

Time to MMR is defined as the time period from the date of first dose intake until the first documented MMR.

Outcome measures

Outcome measures
Measure	Nilotinib n=93 Participants administered orally at a dose of 300 mg twice daily for 24 months
Time to Major Molecular Response (MMR)	252.38 days Standard Deviation 153.22

SECONDARY outcome

Timeframe: 24 months

Population: ITT analysis set. Only participants with a MMR and subsequent loss of MMR were included in the analysis

MMR duration is defined as the time from the date of first documented MMR to the first time of the lost MMR, progression or death.

Outcome measures

Outcome measures
Measure	Nilotinib n=12 Participants administered orally at a dose of 300 mg twice daily for 24 months
Duration of Major Molecular Response (MMR)	91 days Standard Deviation 4.22

Adverse Events

Nilotinib

Serious events: 43 serious events

Other events: 90 other events

Deaths: 2 deaths

Serious adverse events

Serious adverse events
Measure	Nilotinib n=112 participants at risk administered orally at a dose of 300 mg twice daily for 24 months
Cardiac disorders Chest Pain	2.7% 3/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Blood and lymphatic system disorders Acute leukaemia	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Blood and lymphatic system disorders Neutropenia	1.8% 2/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Blood and lymphatic system disorders Thrombocytopenia	3.6% 4/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Cardiac disorders Acute myocardial infarction	1.8% 2/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Cardiac disorders Angina unstable	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Cardiac disorders Bradycardia	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Cardiac disorders Myocardial ischaemia	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Cardiac disorders Paroxysmal arrhythmia	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Eye disorders Conjunctivitis allergic	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Gastrointestinal disorders Abdominal pain	1.8% 2/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Gastrointestinal disorders Oral disorder	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Gastrointestinal disorders Pancreatitis acute	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
General disorders Asthenia	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
General disorders Pyrexia	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Hepatobiliary disorders Hepatitis toxic	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Immune system disorders Hypersensitivity	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Infections and infestations Periorbital cellulitis	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Alanine aminotransferase increased	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Arteriogram coronary	2.7% 3/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Lipase increased	1.8% 2/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Weight decreased	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Musculoskeletal and connective tissue disorders Lumbar vertebral fracture	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Musculoskeletal and connective tissue disorders Pain in extremity	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Musculoskeletal and connective tissue disorders Upper limb fracture	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Nervous system disorders Brain neoplasm	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Pregnancy, puerperium and perinatal conditions Pregnancy	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Skin and subcutaneous tissue disorders Alopecia	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Skin and subcutaneous tissue disorders Pruritus	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Skin and subcutaneous tissue disorders Rash	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Surgical and medical procedures Skin neoplasm excision	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Surgical and medical procedures Uterine dilation and curettage	0.89% 1/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.

Other adverse events

Other adverse events
Measure	Nilotinib n=112 participants at risk administered orally at a dose of 300 mg twice daily for 24 months
Gastrointestinal disorders Abdominal pain upper	5.4% 6/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Alanine aminotransferase increased	10.7% 12/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Skin and subcutaneous tissue disorders Alopecia	5.4% 6/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Amylase increased	6.2% 7/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Blood alkaline phosphatase increased	8.9% 10/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Blood phosphorus decreased	6.2% 7/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Blood triglycerides increased	9.8% 11/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Haemoglobin decreased	6.2% 7/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Investigations Lipase increased	8.0% 9/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Gastrointestinal disorders Constipation	6.2% 7/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Hepatobiliary disorders Hyperbilirubinaemia	15.2% 17/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Hepatobiliary disorders Hypercholesterolaemia	9.8% 11/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Respiratory, thoracic and mediastinal disorders Influenza	11.6% 13/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Blood and lymphatic system disorders Leukopenia	8.9% 10/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Musculoskeletal and connective tissue disorders Myalgia	6.2% 7/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Musculoskeletal and connective tissue disorders Pain in extremity	6.2% 7/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Skin and subcutaneous tissue disorders Pruritus	14.3% 16/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Skin and subcutaneous tissue disorders Rash	11.6% 13/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Blood and lymphatic system disorders Thrombocytopenia	17.0% 19/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.
Respiratory, thoracic and mediastinal disorders Upper respiratory tract infection	7.1% 8/112 • Adverse events were collected from the start of the treatment to end of the treatment i.e 24 months.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER