Phase 2
Completed N=59
Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.
Source: ClinicalTrials.gov NCT01844765 ↗Enrolled (actual)
59
Serious AEs
25.9%
Results posted
May 2018
Primary outcomePrimary: Rate of Major Molecular Response (MMR) at 6 Cycles for Ph+ CML CP Patients Resistant or Intolerant to Imatinib or Dasatinib — 39.4 Percentage of participants
Summary
To evaluate the safety, efficacy and pharmacokinetics of nilotinib over time in the Ph+ chronic myelogenous leukemia (CML) in pediatric patients (from 1 to <18 years).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Rate of Major Molecular Response (MMR) at 6 Cycles for Ph+ CML CP Patients Resistant or Intolerant to Imatinib or Dasatinib |
39.4 | — |
| PRIMARY MMR Rate by 12 Cycles in Newly Diagnosed Ph+ CML-CP Patients |
64.0 | — |
| PRIMARY Rate of Complete Cytogenic Response (CCyR) at 12 Cycles in Newly Diagnosed Ph+ CML-CP Patients |
64.0 | — |
| SECONDARY MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib |
36.4; 45.5; 51.5; 57.6; 57.6; 57.6 | — |
| SECONDARY MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients |
12.0; 52.0; 56.0; 64.0; 68.0; 68.0 | — |
| SECONDARY Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall |
12.1; 15.2; 33.3; 21.2; 9.1; 6.1 | — |
| SECONDARY Best BCR-ABL Ratio Categories for Newly Diagnosed Ph+ CML-CP - Overall |
44.0; 12.0; 20.0; 8.0; 8.0; 8.0 | — |
| SECONDARY Time to First MMR Among Imatinib or Dasatinib Resistant or Intolerant CML-CP Patients Who Achieved MMR |
2.79 | — |
| SECONDARY Time to First MMR Among Newly Diagnosed Ph+ CML-CP Patients Who Achieved MMR |
5.59 | — |
| SECONDARY Duration of First MMR Among Patients Who Were Resistant or Intolerant to Either Imatinib or Dasatinib Who Achieved MMR |
NA | — |
| SECONDARY Duration of First MMR Among Newly Diagnosed Patients Who Achieved MMR |
NA | — |
| SECONDARY Best Complete Cytogenetic Response (CCyR) Categories in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib - Overall |
81.1; 3.0; 3.0; 3.0; 9.1 | — |
| SECONDARY Best Complete Cytogenetic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients - Overall |
84.0 | — |
| SECONDARY Summary of Time to First Complete Cytogenic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients |
5.55 | — |
| SECONDARY Kaplan-Meier Estimates of Time to First Complete Cytogenic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients |
5.6 | — |
| SECONDARY Kaplan-Meier Estimates of Duration of First Complete Cytogenic Response (CCyR) Among Patients Who Achieved CCyR in Newly Diagnosed Ph+ CML-CP Patients |
NA | — |
| SECONDARY Best Major Cytogenetic Response (MCyR) Rate by Time Point in Newly Diagnosed Ph+ CML Patients |
88.0; 88.0; 88.0; 88.0; 88.0; 88.0 | — |
| SECONDARY Summary of Time to First Major Cytogenetic Response (MCyR) Among Patients Who Achieved MCyR in Newly Diagnosed CML-CP Patients |
5.55 | — |
| SECONDARY Kaplan-Meier Estimates of Time to First Major Cytogenetic Response (MCyR) in Newly Diagnosed CML-CP Patients |
5.55 | — |
| SECONDARY Best Complete Hematological Response (CHR) by Time Point |
76.0; 84.0; 88.0; 92.0; 92.0; 92.0 | — |
| SECONDARY Summary of Time to First Complete Hematological Response (CHR) Among Patients Who Achieved Confirmed CHR in Newly Diagnosed CML-CP Patients |
0.95 | — |
| SECONDARY Kaplan-Meier Estimates of Time to First Complete Hematological Response (CHR) in Newly Diagnosed CML-CP Patients |
1.0 | — |
| SECONDARY Time to Disease Progression for Imatinib or Dasatinib Resistant or Intolerant CML-CP Patients - Kaplan-Meier Estimates |
NA | — |
| SECONDARY Event Free Survival in Imatinib/Dasatinib Resistant/Intolerant CML-CP Patients |
NA | — |
| SECONDARY Event Free Survival in Newly Diagnosed CML-CP Patients |
NA | — |
| SECONDARY Overall Survival (OS) in Imatinib/Dasatinib Resistant/Intolerant CML-CP - Kaplan-Meier Estimates |
NA | — |
| SECONDARY Overall Survival (OS) in Newly Diagnosed CML-CP Patients |
NA | — |
| SECONDARY Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle |
36.4; 12.0; 45.5; 52.0; 51.5; 56.0 | — |
| SECONDARY Pharmacokinetics (PK): Steady State Concentration of Nilotinib in Imatinib/Dasatinib Resistant/Intolerant CML-CP Patients |
1407.89 | — |
| SECONDARY Pharmacokinetics: Steady State Concentration of Nilotinib in Newly Diagnosed CML-CP Patients |
1274.30 | — |
| SECONDARY Growth Data: Abnormal Height Standard Deviation Scores (SDS) Changes by Cohort |
27.3; 32.0; 3.0; 16.0; 6.1; 4.0 | — |
| SECONDARY Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation |
75.9; 22.4; 91.4; 6.9; 43.1; 12.1 | — |
| SECONDARY Mutational Assessment of BCR-ABL |
39.4; 32.0; 0.0; 0.0; 0.0; 0.0 | — |
Eligibility Criteria
Key Inclusion Criteria
- Newly diagnosed and untreated Ph+ CML CP or Ph+ CML CP or AP resistant or intolerant to either imatinib or dasatinib
- Karnofsky ≥ 50% for patients > 10 years of age and Lansky ≥ 50 for patients ≤ 10 years of age
- Adequate renal, hepatic and pancreatic function
- Potassium, magnesium, phosphorus and total calcium values ≥ LLN (lower limit of normal)
- Written informed consent
Key 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.
- the criteria regarding pregnancy and contraception
- Active or systemic bacterial, fungal, or viral infection
- known Hepatitis B, Hepatitis C, or HIV infection
Data sourced from ClinicalTrials.gov (NCT01844765). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.