Overview

This trial is active, not recruiting.

Conditions leukemia, leukemia,pediatric, leukemia, myleiod, leukemia, mylegenous, chronic, leukemia, mylegenous, accelerated, bcr-abl positive, myeloproliferative disorder, bone marrow disease, hematologic diseases, neoplastic processes, imatinib, dasatinib, enzyme inhibitor, protein kinase inhibitor
Treatment nilotinib
Phase phase 2
Targets PDGF, BCR-ABL, KIT
Sponsor Novartis Pharmaceuticals
Collaborator Children's Oncology Group
Start date August 2013
End date October 2020
Trial size 59 participants
Trial identifier NCT01844765, CAMN107A2203

Summary

To evaluate the safety, efficacy and concentration of nilotinib over time in the Ph+ chronic myelogenous leukemia (CML) in pediatric patients (from 1 to <18 years).

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
nilotinib Tasigna, AMN107
Nilotinib will be administered at 230mg/m2 ,twice daily for up to 66 cycles (1 cycle = 28 days). Drug will be supplied in 50mg, 150mg,and 200mg capsules. Dose administration will be rounded to the nearest 50mg dose (to a maximum dose of 400mg).
(Experimental)
Resistant or Intolerant to either imatnib or dasatnib
nilotinib Tasigna, AMN107
Nilotinib will be administered at 230mg/m2 ,twice daily for up to 66 cycles (1 cycle = 28 days). Drug will be supplied in 50mg, 150mg,and 200mg capsules. Dose administration will be rounded to the nearest 50mg dose (to a maximum dose of 400mg).
(Experimental)
Resistant or intolerant to either imatnib or dasatnib
nilotinib Tasigna, AMN107
Nilotinib will be administered at 230mg/m2 ,twice daily for up to 66 cycles (1 cycle = 28 days). Drug will be supplied in 50mg, 150mg,and 200mg capsules. Dose administration will be rounded to the nearest 50mg dose (to a maximum dose of 400mg).

Primary Outcomes

Measure
Rate of Major Molecular Responder (MMR) by BCR-ABL RQ-PCR analysis from peripheral blood by 12 cycles
time frame: 12 cycles
Rate of CCyR at 12 cycles
time frame: 12 cycles
Rate of Major Molecular Responder (MMR) by BCR-ABL RQ-PCR analysis from peripheral blood at 6 cycles
time frame: 6 cycles
Rate of Confirmed Hematological Responder (CHR) measured by complete blood count by 3 cycles
time frame: 3 cycles

Secondary Outcomes

Measure
Time to response
time frame: up to 66 cycles
Duration of response
time frame: up to 66 cycles
Time to Disease Progression
time frame: up to 66 cycles
Overall survival (OS)
time frame: up to 66 cycles
Rate of major cytogenetic response (MCyR) and confirmed cytogenetic response (CCyR) in Newly diagnosed Ph+ CML and in Ph+ CML-AP patients resistant/intolerant to either imatinib or dasatinib
time frame: 6, 12, 18, 24, 36, 48, 66 cycles
Pharmacodynamics
time frame: up to 66 cycles
Rate of MMR
time frame: 3, 6, 9,12, 18,24, 36, 48, 66
Event Free Survival
time frame: up to 66 cycles
Rate of Cytogenetic Response category
time frame: 6, 12, 18, 24, 36, 48, 66 cycles
Rate of CHR
time frame: 3,6, 9, 12, 18, 24, 36, 48, 66
PK profile of nilotinib in pediatric patients
time frame: up to 12 cycles
Emerging signs of resistance
time frame: up to 66 cycles
Long term effect of nilotinib on growth, development and maturation
time frame: up to 66 cycles
Further characterize safety and tolerability
time frame: up to 66 cycles
Acceptability of study drug formulation
time frame: day1, day 28, early discontinuation or month 12

Eligibility Criteria

Male or female participants from 1 year up to 17 years old.

Inclusion Criteria: - Newly diagnosed and untreated Ph+ CML CP or Ph+ CML CP or AP resistant or intolerant to either imatinib or dasatinib - Karnofsky or Lansky ≥ 50 - Adequate renal, hepatic and pancreatic function - Potassium, magnesium, phosphorus and total calcium values ≥ LLN (lower limit of normal) - Written informed consent Exclusion Criteria: - Treatment with strong CYP3A4 inhibitors or inducers - Use or planned use of any medications that have a known risk or possible risk to prolong the QT interval - Acute or chronic liver, pancreatic or severe renal disease - History of pancreatitis or chronic pancreatitis. - Impaired cardiac function - No evidence of active graft vs host and <3mo since Stem Cell Transplant - Total body irradiation (TBI) or craniospinal radiation therapy <6months - Hypersensitivity to the active ingredient or any of the excipients including lactose. - Other protocol-defined inclusion/exclusion criteria.

Additional Information

Official title A Multi-center, Open Label, Non-controlled Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Pediatric Patients With Newly Diagnosed Ph+ Chronic Myelogenous Leukemia (CML) in Chronic Phase (CP) or With Ph+ CML in CP or Accelerated Phase (AP) Resistant or Intolerant to Either Imatinib or Dasatinib
Trial information was received from ClinicalTrials.gov and was last updated in October 2016.
Information provided to ClinicalTrials.gov by Novartis.