Clinical trial NCT02108951: Study to Assess Efficacy and Safety of Nilotinib 300mg Twice Daily in Patients With Philadelphia Positive Chronic Myeloid Leukaemia (CML) in Chronic Phase Who Are Intolerant to Prior Tyrosine Kinase Inhibitors.
Official title: A Multicenter, Single Arm Study to Assess Efficacy and Safety of Nilotinib 300mg Twice Daily in Patients With Philadelphia Positive Chronic Myeloid Leukemia in Chronic Phase (Ph+ CML-CP) Who Are Intolerant to Prior Tyrosine Kinase Inhibitors (TKIs).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Philidelphia Positive Chronic Myeloid Leukaemia
Keywords: CML
Ph-CML
leukaemia
leukemia
chronic myeloid leukemia
chronic myeloid leukaemia
TKI intolerance
tyrosine kinase inhibitor
tyrosine kinase inhibitor intolerance
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2014-04-09
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this Australian study was to assess the efficacy and safety of nilotinib 300mg twice daily in patients with chronic myeloid leukemia chronic phase who were intolerant but responsive to 1st line treatment with imatinib or dasatinib. Eligible patients have been previously treated with imatinib or dasatinib for at least 3 months and are experiencing non-hematologic toxicity whilst having documented responses that meet PBS authority for 1st line treatment of CML without current MR4.5.

Detailed description: The study was planned to enroll 130 patients to achieve the sample size requirement for a meaning full conclusion. Study got terminated with 20 patients because of slow recruitment. Therefore, due to small sample size, the results cannot be considered clinical significant.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent prior to screening procedures
2. Eastern Cooperative Oncology Grou (ECOG) Performance Status of 0, 1, or 2.
3. Patient with diagnosis of Ph+ CML-CP associated with BCR-ABL quantifiable by RQ-PCR (IS).
4. Patient has received a minimum of 3 months of imatinib or dasatinib treatment (any dose) since initial diagnosis with a documented response.
5. Patient is eligible for Pharmaceutical Benefits Scheme (PBS) reimbursed 1st line TKI treatment.
6. Patient has experienced non-hematological Adverse Events (AE(s)) of any grade, which persisted for at least 1 month despite supportive care or recurred at any grade at least once. Patients who, at the Investigator's discretion, require immediate discontinuation due to the severity of the adverse event are also eligible.
7. No other current or planned anti-leukemia therapies.
8. Adequate organ function.
9. Potassium, Magnesium and Total Calcium above Lower limit of normal.
10. life expectancy of more than 12 months in the absence of any intervention

Key Exclusion Criteria:

1. Prior treatment with nilotinib.
2. Prior Accelerated Phase (AP), Blast Crisis (BC) or allogeneic-transplant (unless the patient received an autologous transplant and was in Chrionic Phase (CP) prior to transplant and never in AP or BC).
3. Patient has documented Molecular Response (MR) 4.5 at the time of study entry
4. Patients with atypical BCR-ABL transcript not quantifiable by standard RQ-PCR.
5. Known impaired cardiac function.
6. Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug.
7. Pregnant or breast feeding (lactating) women.
8. Women of child-bearing potential unwilling or unable to use highly effective contraception.

Primary outcomes:
measure: Deep Molecular Response (MR4.5) Rate: Percentage of Patients Who Have Achieved a 4.5-log Reduction in BCR-ABL Level Within 24 Month
timeFrame: Baseline, 96 weeks (24 months)
measure: Molecular Response (MR4.0) Rate: Percentage of Patients Who Have Achieved a 4.0-log Reduction in BCR-ABL Level Within 12 Months and 24 Months
timeFrame: Baseline, 48 weeks (12 months), 96 weeks (24 months)
measure: Major Molecular Response (MMR) Rate: Percentage of Patients Who Have Achieved a 3 Log Reduction in BCR-ABL Levels Within 12 Months and 24 Months
timeFrame: Baseline, 48 weeks (12 months), 96 weeks (24 months)
measure: Duration of Prior TKI Therapy for Patients Based on MR4.5 Achievement Status Within 24 Months
timeFrame: Baseline, 96 weeks (24 months)
measure: Number of Patients With MR4.5 Response by Baseline BCR-ABL Response Level Within 24 Months
timeFrame: Baseline, 96 weeks (24 months)
Secondary outcomes:
measure: Kinetics of Molecular Response: Percentage of Patients With no Response Based on BCR-ABL Over Time After the Switch to Nilotinib
timeFrame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
measure: Kinetics of Molecular Response: Percentage of Patients With MMR Based on BCR-ABL Over Time After the Switch to Nilotinib
timeFrame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72 and 96
measure: Kinetics of Molecular Response: Percentage of Patients With MR4.0 Based on BCR-ABL Over Time After the Switch to Nilotinib
timeFrame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
measure: Kinetics of Molecular Response: Percentage of Patients With MR4.5 Based on BCR-ABL Over Time After the Switch to Nilotinib
timeFrame: Baseline, week 4, 8, 12, 24, 36, 48, 60, 72, 84, 96
measure: Kaplan-Meier Estimates of Time to Deep Molecular Response (MR4.5)
timeFrame: 96 weeks (24 months)
measure: Time to Progression-free Survival (PFS)
timeFrame: 96 weeks (24 months)
measure: Time to Event Free Survival (EFS)
timeFrame: 96 weeks (24 months)
measure: Number of Patients With Events Reported at Baseline That Have Shown an Improvement in Non-hematological AE Severity Compared to Week 12 Visit
timeFrame: Baseline, week 12 (month 3)
measure: Mean M.D. Anderson Symptom Inventory - Chronic Myeloid Leukemia (MDASI-CML)
timeFrame: Baseline, week 12, 24, 48, 96
Other outcomes:
Locations:
city: Canberra
country: Australia
facility: Novartis Investigative Site
state: Australian Capital Territory
city: Kingswood
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Kogarah
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Liverpool
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: St. Leonards
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Douglas
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Nambour
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: South Brisbane
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Adelaide
country: Australia
facility: Novartis Investigative Site
state: South Australia
city: Fitzroy
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Geelong
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Melbourne
country: Australia
facility: Novartis Investigative Site
state: Victoria
city: Murdoch
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: