Acute Lymphoblastic Leukemia (ALL), Chronic Myelogenous Leukemia (CML), Metastatic Gastrointestinal Stromal Tumors (GIST), Receptor Tyrosine Kinase (KIT) Mutated Melanoma
Conditions
Keywords
metastatic gastrointestinal stromal tumors (GIST), Philadelphia chromosome positive (Ph+) chronic myelogenous leukemia in chronic phase (CML-CP),, adult, Chronic myelogenous leukemia (CML), chronic myeloid leukemia (CML), chronic myelocytic leukemia (CML), Acute Lymphoblastic Leukemia (ALL), Philadelphia chromosome positive, Acute Lymphoid Leukemia, suboptimal molecular response, Tasigna, CML, GIST, nilotinib
Brief summary
The purpose of this study was to allow continued use of nilotinib in patients who were on nilotinib treatment in a Novartis-sponsored, Oncology Clinical Development & Medical Affairs (CD&MA) study and were benefiting from the treatment as judged by the investigator
Detailed description
This was a multi-center, open label, single-arm, phase IV study to better characterize the long-term safety of nilotinib in patients treated in Novartis-sponsored studies and who benefited from treatment with nilotinib. Patients who were enrolled in Novartis-sponsored nilotinib studies, had benefitted from treatment with nilotinib and fulfilled all requirements in the parent study could be enrolled into the current roll-over study. There was no sample size estimation carried out for this study. Patients returned to the study center on a quarterly basis (12 weeks ± 1 week) for scheduled visit. Adverse Events (AEs) (non-serious and serious AEs), clinical benefit assessment by investigator and study medication dispensing information were collected. The original protocol of the current roll-over study was designed to provide continuation of treatment with nilotinib for patients enrolled in nilotinib studies. Therefore, the original protocol did not require AEs (non-serious and serious AEs) to be collected into the clinical database and only required serious adverse events (SAEs) to be collected in the Novartis safety database throughout the study duration. The scheduled visit frequency was annually. However, feedback from health authorities stated that all AEs should be collected. To account for this, the protocol was amended in 2016 (Protocol amendment 3 (PA 3)), with the primary objective changed to assess long-term safety of nilotinib. Consequently, PA 3 started to require all AEs (non-serious and serious AEs) to be entered into the clinical database, in addition to the continued SAE collection into the Novartis safety database. At the same time, the scheduled visit frequency was increased from annually to quarterly, and the protocol was also amended to require an investigator assessment of clinical benefit for patients.
Interventions
DRUGNilotinib
Patients who were on nilotinib treatment in a Novartis-sponsored study (parent study) and were benefiting from nilotinib treatment met the criteria for enrolment into the CAMN107A2409 study and to receive continued nilotinib treatment. The starting dose of nilotinib in the CAMN107A2409 study should have been the same as the last dose administered in the parent study. After the starting dose, the dose of nilotinib was based on the investigator's judgement. The dose of nilotinib should have been ≤ 800 mg/day for adult patients, 230mg/m2 body surface area (BSA) and ≤ 800 mg/day for pediatric patients.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
-Patient is currently enrolled in a Novartis-sponsored, Oncology Clinical Development & Medical Affairs study receiving nilotinib and has fulfilled all their requirements in the parent study -Patient is currently benefiting from the treatment with nilotinib, as determined by the investigator -Patient has demonstrated compliance, as assessed by the investigator, with the parent study protocol requirements -Willingness and ability to comply with scheduled visits, treatment plans and any other study procedures -Written informed consent obtained prior to enrolling in roll-over study
Exclusion criteria
\- Patient has been permanently discontinued from nilotinib treatment in the parent study due to unacceptable toxicity, non-compliance to study procedures, withdrawal of consent or any other reason - Patient has participated in a Novartis sponsored combination trial where nilotinib was dispensed in combination with another study medication and patient is still receiving combination therapy -Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval or inducing Torsade de Pointes and the treatment cannot be either safely discontinued at least one week prior to nilotinib treatment or switched to a different medication prior to start of nilotinib treatment and for the duration of the study -Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive hcG laboratory test. -Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the study and for 30 days after the final dose of nilotinib.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events and Serious Adverse Events | SAE case data were collected the entire study duration after first dose of study treatment up to a max. time of approx. 10 yrs. AEs (both non-serious and serious) were collected in the eCRF 3 yrs after study initiation up to a max. time of approx. 7 yrs. | An Adverse Event (AE) is any untoward medical occurrence (eg any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Serious adverse event (SAE) case data were collected in the Safety Database. Adverse event (AE) data (both non-serious and serious) were collected in the Clinical database. Max. = Maximum Yrs = Years Approx. = Approximately eCRF = electronic Case Report Form Time = timeframe |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Clinical Benefit From Nilotinib | Clinical benefit data were first collected 3 years after study initiation and are reported at baseline, Weeks 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 528. | Number of patients (pts) with clinical benefit as assessed by investigator. Clinical benefit data were first collected 3 years after study initiation and up to a maximum timeframe of approx. 7 years and 3 months at a patient level (up to Week 528 total at the study level). Pts who discontinued in the first 3 years after study initiation didn't have any clinical benefit data collected. Pts who enrolled in the first 3 years after study initiation only had clinical benefit data collected starting at approx. the third year of the study until the end of the patient's participation in the study. Pts who enrolled after the first 3 years after study initiation had all clinical benefit data collected until the end of the patient's participation in the study. Data for the earlier time points are provided only for later enrolled pts. Data for the later time points are provided only for the earlier enrolled pts. The time point per patient was calculated from the date of first drug intake. |
Countries
Austria, Canada, France, Hong Kong, Hungary, Israel, Italy, Netherlands, Russia, Singapore, Slovakia, South Korea, Spain, Sweden, United Kingdom, United States
Participant flow
Pre-assignment details
The study had no screening period. In total, 57 patients were enrolled and treated with nilotinib on this study. Patients were rolled over from 5 parent studies with the following indications: Chronic myelogenous leukemia (CML), Metastatic gastrointestinal stromal tumors (GIST), Acute lymphoblastic leukemia (ALL), and Receptor tyrosine kinase (KIT) mutated melanoma.
Participants by arm
| Arm | Count |
|---|---|
| Nilotinib Adult patients: ≤ 800mg/day; Pediatric patients: 230mg/m2 twice daily (BID) and ≤ 800mg/day | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Administrative problems | 1 |
| Overall Study | Adverse Event | 5 |
| Overall Study | Disease progression | 24 |
| Overall Study | Patient/guardian decision | 1 |
| Overall Study | Patient withdrew consent | 2 |
| Overall Study | Physician Decision | 4 |
Baseline characteristics
| Characteristic | Nilotinib | — |
|---|---|---|
| Age, Categorical <=18 years | 7 Participants | — |
| Age, Categorical >=65 years | 20 Participants | — |
| Age, Categorical Between 18 and 65 years | 30 Participants | — |
| Age, Continuous | 53.02 years STANDARD_DEVIATION 19.278 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 30 Participants | — |
| Sex: Female, Male Male | 27 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 57 |
| other Total, other adverse events | 20 / 57 |
| serious Total, serious adverse events | 17 / 57 |
Outcome results
Primary
Number of Participants With Adverse Events and Serious Adverse Events
An Adverse Event (AE) is any untoward medical occurrence (eg any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Serious adverse event (SAE) case data were collected in the Safety Database. Adverse event (AE) data (both non-serious and serious) were collected in the Clinical database. Max. = Maximum Yrs = Years Approx. = Approximately eCRF = electronic Case Report Form Time = timeframe
Time frame: SAE case data were collected the entire study duration after first dose of study treatment up to a max. time of approx. 10 yrs. AEs (both non-serious and serious) were collected in the eCRF 3 yrs after study initiation up to a max. time of approx. 7 yrs.
Population: safety set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Nilotinib | Number of Participants With Adverse Events and Serious Adverse Events | Adverse Events - total | 29 Participants |
| Nilotinib | Number of Participants With Adverse Events and Serious Adverse Events | Adverse Events - Treatment-related adverse events | 15 Participants |
| Nilotinib | Number of Participants With Adverse Events and Serious Adverse Events | SAEs - total | 17 Participants |
| Nilotinib | Number of Participants With Adverse Events and Serious Adverse Events | SAEs - Treatment-related SAEs | 2 Participants |
| Nilotinib | Number of Participants With Adverse Events and Serious Adverse Events | AEs leading to discontinuation - total | 3 Participants |
| Nilotinib | Number of Participants With Adverse Events and Serious Adverse Events | AEs leading to discontinuation - Treatment-related AEs leading to discontinuation | 3 Participants |
Secondary
Number of Participants With Clinical Benefit From Nilotinib
Number of patients (pts) with clinical benefit as assessed by investigator. Clinical benefit data were first collected 3 years after study initiation and up to a maximum timeframe of approx. 7 years and 3 months at a patient level (up to Week 528 total at the study level). Pts who discontinued in the first 3 years after study initiation didn't have any clinical benefit data collected. Pts who enrolled in the first 3 years after study initiation only had clinical benefit data collected starting at approx. the third year of the study until the end of the patient's participation in the study. Pts who enrolled after the first 3 years after study initiation had all clinical benefit data collected until the end of the patient's participation in the study. Data for the earlier time points are provided only for later enrolled pts. Data for the later time points are provided only for the earlier enrolled pts. The time point per patient was calculated from the date of first drug intake.
Time frame: Clinical benefit data were first collected 3 years after study initiation and are reported at baseline, Weeks 24, 48, 72, 96, 144, 192, 240, 288, 336, 384, 432, 480, and 528.
Population: Safety set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week144 | 23 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 336 | 9 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 384 | 7 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Baseline | 15 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 24 | 11 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 48 | 17 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 72 | 11 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 96 | 19 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 192 | 26 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 240 | 20 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 288 | 9 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 432 | 6 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 480 | 6 Participants |
| Nilotinib | Number of Participants With Clinical Benefit From Nilotinib | Patients with clinical benefit - Week 528 | 4 Participants |