Adult patients treated with a planned dose of nilotinib 300 mg BID (or at a reduced dose level of 400 mg QD if required from the perspective of tolerance) for a minimum of 2 calendar years for newly diagnosed BCR-ABL positive Chronic Myelogenous Leukemia in chronic phase and have achieved MR 4.5 (BCR-ABL = 0.0032% IS) at any time point before being enrolled in the study MedDRA version: 21.0 Level: LLT Classification code 10054352 Term: Chronic phase chronic myeloid leukemia System Organ Class:
Conditions
Interventions
Trade Name: Tasigna
Product Name: Tasigna
Product Code: AMN107
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: NILOTINIB
CAS Number: 641571-10-0
Current Sponsor code: AMN107
Concentration unit
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for inclusion in this study have to meet all of the following criteria; additional inclusion criteria may apply as per protocol: 1) Male or female patients =18 years of age 2) Minimum of 2 calendar years of nilotinib treatment with at least the last 12 months of nilotininb treatment prior to pre-screening at the approved total daily dose of 600 mg or at a reduced dose of 400 mg QD if required from the perspective of tolerance for BCR-ABL positive CML in documented chronic phase at the time of diagnosis 3) Evidence of typical BCR-ABL transcripts [b3a2 (e14a2) and/or b2a2 (e13a2)] at the time of CML-CP diagnosis i.e. prior to first start of TKI treatment which are amenable to standardized RT-PCR quantification” 4) Patient in MR4.5 at prescreening at Novartis designated lab 5) ECOG performance status of 0-2 6) Adequate end organ function as defined by: • Direct bilirubin = 1.5 x ULN, except for i) patients with documented Gilbert’s syndrome for whom any bilirubin value is allowed and ii) for patients with asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase within normal range) • SGOT(AST) and SGPT(ALT) = 3 x ULN i.e. equivalent to = Grade 1 NCI-CTCAE v.4.03 • Serum lipase = 2 x ULN i.e. equivalent to = Grade 2 NCI-CTCAE v.4.03 • Alkaline phosphatase = 2.5 x ULN • Serum creatinine =65 years) yes F.1.3.1 Number of subjects for this age range 44
Exclusion criteria
Exclusion criteria: Patients eligible for this study must not meet any of the following criteria: 1) Previous treatment with BCR-ABL inhibitors other than nilotinib for more than a total cumulative duration of 4 weeks 2) Previous treatment with alpha-interferon of any duration 3) Previous anticancer agents for CML other than nilotinib except for cytoreduction after CML diagnosis until up to 4 weeks after first dose of nilotinib 4) Known second chronic phase of CML after previous progression to AP/BC 5) Poorly controlled diabetes mellitus (defined as HbA1c > 9%) 6) Impaired cardiac function as defined in the protocol 7) History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis 8) Known presence of significant congenital or acquired bleeding disorder unrelated to cancer 9) History of another active malignancy within 5 years prior to study entry with the exception of previous or concomitant basal cell skin cancer and previous carcinoma in situ treated curatively 10) Treatment with other investigational agents (defined as not used in accordance with the approved indication) within 4 weeks of Day 1 11) Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. 12) Patients actively receiving therapy with herbal medicines that are strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug. These herbal medicines may include Echinacea, (including E. purpurea, E. angustifolia and E. pallida), Piperine, Artemisinin, St. John’s Wort, and Ginkgo. 13) Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug. (Please see http://crediblemeds.org/everyone/composite-list-all-qtdrugs/ for a list of agents that prolong the QT interval) 14) Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery) 15) 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. 16) 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 14 days after the final dose of nilotinib. Highly effective contraception is defined in the protocol. Additional exclusion criteria are defined in the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine the percentage of patients who are in Major Molecular Response (MMR) at 48 weeks after starting the treatment-free remission (TFR) phase (patients who required re-initiation of treatment will be considered as non-responders) ;Secondary Objective: 1) To determine the percentage of patients who are in MR4.5 (BCR-ABL = 0.0032% IS) at 48 weeks after starting the TFR phase (patients who required re-initiation of treatment will be considered as non-responders) 2) To determine the percentage of patients who are in MMR at 96, 144, 192, 264 weeks, and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase (patients who required re-initiation of treatment will be considered as non-responders) 3) To determine the percentage of patients who are in MR4.5 at 96, 144, 192, 264 weeks, and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase (patients who required re-initiation of treatment will be considered as non-responders) 4) To determine the percentage of patients in MMR at 48, 96, 144, 192, 264 weeks, and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase of nilotinib irrespective of whether or not patients required reinitiation of treatment Additional objectives apply.;Primary end point(s): BCR-ABL = 0.1% IS (MMR or MR3) at 48 weeks after starting the treatment-free remission (TFR) phase with no loss of MMR and no re-initiation of nilotinib therapy in the first 48 weeks after starting the TFR phase. ;Timepoint(s) of evaluation of this end point: 48 weeks after starting the TFR phase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) BCR-ABL = 0.0032% IS (MR4.5) at 48 weeks after starting the treatment-free remission (TFR) phase with no loss of MR4.5 and no reinitiation of nilotinib therapy in the first 48 weeks after starting the TFR phase. 2) BCR-ABL = 0.1% IS (MMR) at 96, 144, 192, 264 weeks, and at the end of 6, 7, 8, 9, and 10 years after starting the TFR phase with no loss of MMR and no re-initiation of nilotinib therapy in the first 96, 144, 192, 264 weeks , and in the firsts 6, 7, 8, 9, and 10 years after starting the TFR phase. 3) BCR-ABL = 0.0032% IS (MR4.5) at 96, 144, 192, 264 weeks, and at the end of 6, 7, 8, 9, and 10 years after starting the TFR phase with no loss of MR4.5 and no re-initiation of nilotinib therapy in the first 96, 144, 192, 264 weeks, and in the first 6, 7, 8, 9, and 10 years after starting the TFR phase. 4) BCR-ABL = 0.1% IS (MMR) at 48, 96, 144, 192, 264 weeks, and at the end of 6, 7, 8, 9 and 10 years after starting the TFR phase.;Timepoint(s) of evaluation of this end point: 1) at 48 weeks after starting the TFR phase. 2) - 4) at 96, 144, 192, 264 weeks, and at the end of 6, 7, 8, 9, and 10 years after starting the TFR. | — |
Countries
Argentina, Austria, Belgium, Bulgaria, Colombia, Denmark, France, Germany, Greece, Hungary, Ireland, Italy, Japan, Netherlands, Poland, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactDrug Regulatory Affairs
Novartis Pharma GmbH
Outcome results
None listed