Trial Outcomes & Findings for CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib (NCT NCT01227577)
NCT ID: NCT01227577
Last Updated: 2016-02-08
Results Overview
CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl \<=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.
COMPLETED
PHASE4
128 participants
4 years
2016-02-08
Participant Flow
Participant milestones
| Measure |
Nilotinib
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Overall Study
STARTED
|
128
|
|
Overall Study
COMPLETED
|
93
|
|
Overall Study
NOT COMPLETED
|
35
|
Reasons for withdrawal
| Measure |
Nilotinib
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Overall Study
Protocol deviation
|
3
|
|
Overall Study
Death
|
3
|
|
Overall Study
Administrative problems
|
2
|
|
Overall Study
Lost to Follow-up
|
1
|
|
Overall Study
Withdrawal by Subject
|
4
|
|
Overall Study
Lack of Efficacy
|
5
|
|
Overall Study
Adverse Event
|
17
|
Baseline Characteristics
CMR Rate of Newly Diagnosed CML-CP Patients Treated With Nilotinib
Baseline characteristics by cohort
| Measure |
Nilotinib
n=128 Participants
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Age, Continuous
|
55.6 Years
STANDARD_DEVIATION 14.99 • n=5 Participants
|
|
Sex: Female, Male
Female
|
64 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
64 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 4 yearsPopulation: Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study drug.
CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl \<=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.
Outcome measures
| Measure |
Nilotinib
n=128 Participants
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Number of Participants With Confirmed Complete Molecular Response (CMR)
|
34 Participants
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study drug.
CCyR was defined as 0% Philadelphia chromosome-positive (Ph+) metaphases in the bone marrow. MMR was defined as a 3 log reduction of Bcr-Abl transcripts from the standardized baseline on the international scale (equivalent to Bcr-Abl ≤ 0.1% IS). Bcr-Abl transcripts assessed by peripheral blood quatitative real time polymerase chain reaction (RQ-PCR) were used for the determination of all molecular responses.
Outcome measures
| Measure |
Nilotinib
n=128 Participants
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Number of Participants With Complete Cytogenetic Response (CCyR) and Major Molecular Response (MMR)
CCyR
|
93 Participants
|
|
Number of Participants With Complete Cytogenetic Response (CCyR) and Major Molecular Response (MMR)
MMR
|
94 Participants
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: Of the 128 participants analyzed, 34 participants achieved CMR within 18 months of treatment, 93 participants achieved CCyR and did not experience loss of CCyR during the study, and 94 participants achieved MMR with up to 24 months of treatment (most achieved MMR within 12 months of treatment).
Time to CMR, CCyR, and MMR was defined as the time from the date of enrollment to the date of first documented CMR, CCyR and MMR, respectively.
Outcome measures
| Measure |
Nilotinib
n=128 Participants
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Time to CMR, CCyR and MMR
CMR (n=34)
|
NA Months
The median could not be calculated due to insufficient events.
|
|
Time to CMR, CCyR and MMR
CCyR (n=93)
|
5.5 Months
Interval 4.07 to 5.55
|
|
Time to CMR, CCyR and MMR
MMR (n=94)
|
5.7 Months
Interval 5.55 to 7.66
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: Of the 128 participants analyzed, 34 participants achieved CMR within 18 months of treatment, 93 participants achieved CCyR and did not experience loss of CCyR during the study, and 94 participants achieved MMR with up to 24 months of treatment (most achieved MMR within 12 months of treatment).
Duration of CMR, CCyR and MMR were defined as the time from the first date of achievement of the response to the date of first documented loss of the response.
Outcome measures
| Measure |
Nilotinib
n=128 Participants
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Duration of CMR, CCyR and MMR
CMR (n=34)
|
7.97 Months
Standard Deviation 3.705
|
|
Duration of CMR, CCyR and MMR
CCyR (n=93)
|
NA Months
Standard Deviation NA
None of the participants experienced loss of CCyR during the study.
|
|
Duration of CMR, CCyR and MMR
MMR (n=94)
|
4.86 Months
Standard Deviation 5.003
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study drug.
Progression to AP/BC is defined as loss of CCyR, MMR, and CMR and was summarized by frequencies and percentages.
Outcome measures
| Measure |
Nilotinib
n=128 Participants
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Number of Participants With Progression to Accelerated Phase/Blastic Crisis (AP/BC)
|
1 Participants
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: Of the 128 participants analyzed, 1 participant experienced progression to AP/BC.
Time to progression of AP/BC was defined as the time from the date of the first dose of study drug to the date of first documented progression of AP/BC.
Outcome measures
| Measure |
Nilotinib
n=128 Participants
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Time to Progression of AP/BC
|
NA Months
The median could not be calculated due to an insufficient number of events.
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: Numbers are based on the total number of participants who achieved and experienced loss of CMR (34 participants), CCyr (93 participants) and MMR (94 participants), respectively.
Rate of loss of CMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.0032% IS. Rate of loss of CCyR was defined as an increase in the Ph+ bone marrow cells to greater than 0%. Rate of loss of MMR was defined as an increase in the Bcr-Abl transcripts to greater than 0.1% IS.
Outcome measures
| Measure |
Nilotinib
n=128 Participants
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Number of Participants With Loss of CCyR, MMR and CMR
MMR (n=94)
|
13 Participants
|
|
Number of Participants With Loss of CCyR, MMR and CMR
CMR (n=34)
|
6 Participants
|
|
Number of Participants With Loss of CCyR, MMR and CMR
CCyR (n=93)
|
0 Participants
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: Of the 128 participants analyzed, 3 participants received an escalated dose of 400 mg b.i.d.
CMR was defined as at least 4.5 log reduction of breakpoint cluster region gene/Abelson proto-oncogene (Bcr-Abl) transcipts from the standardized baseline on the international scale (equivalent to Bcr-Abl \<=0.0032% IS) with a minimum of 25,614 ABL control copies. CMR was to be confirmed by a second polymerase chain reaction (PCR) sample drawn 3 months later where the results should be less than or equal to 0.0032% with a minimum of 25,614 Abelson proto-oncogene (ABL) control copies.
Outcome measures
| Measure |
Nilotinib
n=3 Participants
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Number of Participants With CMR Who Were Dosed to 400 mg b.i.d.
|
0 Participants
|
SECONDARY outcome
Timeframe: 4 yearsPopulation: Full Analysis Set (FAS): The FAS included all randomized participants who received at least one dose of study drug.
Event-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: loss of Complete Hematological Response (CHR), loss of CCyR, loss of Partial Cytogenetic Response (PCyR), progression to the accelerated phase or blast crisis, and death from any cause. Progression-free survival was defined as the time from the date of enrollment to the date of first occurrence of any of the following: progression to the accelerated phase or blast crisis, death, and loss of CMR. Overall survival was defined as the time from the date of enrollment until death due to any cause.
Outcome measures
| Measure |
Nilotinib
n=128 Participants
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Event-free Survival, Progression-free Survival and Overall Survival
Event-free
|
NA Months
Median could not be calculated due to an insuffient number of events.
|
|
Event-free Survival, Progression-free Survival and Overall Survival
Progression-free
|
NA Months
Median could not be calculated due to an insuffient number of events.
|
|
Event-free Survival, Progression-free Survival and Overall Survival
Overall
|
NA Months
Median could not be calculated due to an insuffient number of events.
|
Adverse Events
Nilotinib
Serious adverse events
| Measure |
Nilotinib
n=128 participants at risk
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Blood and lymphatic system disorders
Neutropenia
|
1.6%
2/128
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.6%
2/128
|
|
Cardiac disorders
Atrial fibrillation
|
0.78%
1/128
|
|
Cardiac disorders
Myocardial infarction
|
2.3%
3/128
|
|
Cardiac disorders
Palpitations
|
0.78%
1/128
|
|
Endocrine disorders
Hyperthyroidism
|
0.78%
1/128
|
|
Endocrine disorders
Toxic nodular goitre
|
0.78%
1/128
|
|
Gastrointestinal disorders
Abdominal pain
|
3.1%
4/128
|
|
Gastrointestinal disorders
Gastritis
|
0.78%
1/128
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.78%
1/128
|
|
Gastrointestinal disorders
Nausea
|
0.78%
1/128
|
|
Gastrointestinal disorders
Oesophagitis
|
0.78%
1/128
|
|
Gastrointestinal disorders
Pancreatitis
|
2.3%
3/128
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.78%
1/128
|
|
Gastrointestinal disorders
Vomiting
|
0.78%
1/128
|
|
General disorders
Chest pain
|
1.6%
2/128
|
|
General disorders
Pyrexia
|
0.78%
1/128
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.78%
1/128
|
|
Infections and infestations
Device related infection
|
0.78%
1/128
|
|
Infections and infestations
Gastroenteritis
|
0.78%
1/128
|
|
Infections and infestations
Gastroenteritis viral
|
0.78%
1/128
|
|
Infections and infestations
Pharyngitis streptococcal
|
0.78%
1/128
|
|
Infections and infestations
Pneumonia
|
2.3%
3/128
|
|
Infections and infestations
Sepsis
|
0.78%
1/128
|
|
Infections and infestations
Upper respiratory tract infection
|
0.78%
1/128
|
|
Injury, poisoning and procedural complications
Fall
|
0.78%
1/128
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
0.78%
1/128
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.78%
1/128
|
|
Musculoskeletal and connective tissue disorders
Flank pain
|
0.78%
1/128
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.78%
1/128
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anaplastic astrocytoma
|
0.78%
1/128
|
|
Nervous system disorders
Central nervous system lesion
|
0.78%
1/128
|
|
Nervous system disorders
Cerebrovascular accident
|
0.78%
1/128
|
|
Nervous system disorders
Hypoaesthesia
|
0.78%
1/128
|
|
Nervous system disorders
Migraine
|
0.78%
1/128
|
|
Nervous system disorders
Neurological symptom
|
0.78%
1/128
|
|
Nervous system disorders
Sciatica
|
0.78%
1/128
|
|
Nervous system disorders
Syncope
|
0.78%
1/128
|
|
Nervous system disorders
Transient ischaemic attack
|
0.78%
1/128
|
|
Psychiatric disorders
Depression
|
0.78%
1/128
|
|
Psychiatric disorders
Mental status changes
|
0.78%
1/128
|
|
Renal and urinary disorders
Renal failure acute
|
0.78%
1/128
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.78%
1/128
|
|
Respiratory, thoracic and mediastinal disorders
Hiccups
|
0.78%
1/128
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.78%
1/128
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.78%
1/128
|
|
Surgical and medical procedures
Thyroidectomy
|
0.78%
1/128
|
Other adverse events
| Measure |
Nilotinib
n=128 participants at risk
Participants received 300 mg twice daily (b.i.d.). Dose increases to 400 b.i.d. were permitted, per Investigator's discretion.
|
|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
17.2%
22/128
|
|
Blood and lymphatic system disorders
Leukopenia
|
5.5%
7/128
|
|
Blood and lymphatic system disorders
Neutropenia
|
10.2%
13/128
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
14.1%
18/128
|
|
Cardiac disorders
Palpitations
|
6.2%
8/128
|
|
Gastrointestinal disorders
Abdominal distension
|
5.5%
7/128
|
|
Gastrointestinal disorders
Abdominal pain
|
18.8%
24/128
|
|
Gastrointestinal disorders
Abdominal pain upper
|
9.4%
12/128
|
|
Gastrointestinal disorders
Constipation
|
23.4%
30/128
|
|
Gastrointestinal disorders
Diarrhoea
|
22.7%
29/128
|
|
Gastrointestinal disorders
Dry mouth
|
10.2%
13/128
|
|
Gastrointestinal disorders
Dyspepsia
|
7.8%
10/128
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
5.5%
7/128
|
|
Gastrointestinal disorders
Nausea
|
35.2%
45/128
|
|
Gastrointestinal disorders
Vomiting
|
18.0%
23/128
|
|
General disorders
Asthenia
|
5.5%
7/128
|
|
General disorders
Chest pain
|
6.2%
8/128
|
|
General disorders
Fatigue
|
45.3%
58/128
|
|
General disorders
Oedema peripheral
|
7.0%
9/128
|
|
General disorders
Pyrexia
|
6.2%
8/128
|
|
Hepatobiliary disorders
Hyperbilirubinaemia
|
7.0%
9/128
|
|
Infections and infestations
Bronchitis
|
6.2%
8/128
|
|
Infections and infestations
Sinusitis
|
7.0%
9/128
|
|
Infections and infestations
Upper respiratory tract infection
|
16.4%
21/128
|
|
Infections and infestations
Urinary tract infection
|
6.2%
8/128
|
|
Investigations
Alanine aminotransferase increased
|
14.8%
19/128
|
|
Investigations
Amylase increased
|
7.8%
10/128
|
|
Investigations
Aspartate aminotransferase increased
|
8.6%
11/128
|
|
Investigations
Blood bilirubin increased
|
13.3%
17/128
|
|
Investigations
Lipase increased
|
24.2%
31/128
|
|
Investigations
Weight increased
|
6.2%
8/128
|
|
Investigations
White blood cell count decreased
|
5.5%
7/128
|
|
Metabolism and nutrition disorders
Decreased appetite
|
13.3%
17/128
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
7.0%
9/128
|
|
Metabolism and nutrition disorders
Hypomagnesaemia
|
6.2%
8/128
|
|
Metabolism and nutrition disorders
Hypophosphataemia
|
6.2%
8/128
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
19.5%
25/128
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
7.8%
10/128
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
7.0%
9/128
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
17.2%
22/128
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
18.0%
23/128
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
9.4%
12/128
|
|
Nervous system disorders
Dizziness
|
18.0%
23/128
|
|
Nervous system disorders
Headache
|
24.2%
31/128
|
|
Nervous system disorders
Hypoaesthesia
|
10.9%
14/128
|
|
Nervous system disorders
Paraesthesia
|
7.0%
9/128
|
|
Nervous system disorders
Somnolence
|
6.2%
8/128
|
|
Psychiatric disorders
Anxiety
|
9.4%
12/128
|
|
Psychiatric disorders
Depression
|
7.8%
10/128
|
|
Psychiatric disorders
Insomnia
|
11.7%
15/128
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
11.7%
15/128
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
20.3%
26/128
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
9.4%
12/128
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
17.2%
22/128
|
|
Skin and subcutaneous tissue disorders
Dry skin
|
14.1%
18/128
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
7.0%
9/128
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
15.6%
20/128
|
|
Skin and subcutaneous tissue disorders
Rash
|
37.5%
48/128
|
Additional Information
Study Director
Novartis
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 (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER