TriangleNCT01844765 · CITED IN SOURCE DOCUMENTS
Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE2
- Status at capture
- COMPLETED
- Registry last update
- 2021-04-22
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).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Rate of Major Molecular Response (MMR) at 6 Cycles for Ph+ CML CP Patients Resistant or Intolerant to Imatinib or Dasatinib
MMR Rate by 12 Cycles in Newly Diagnosed Ph+ CML-CP Patients
Rate of Complete Cytogenic Response (CCyR) at 12 Cycles in Newly Diagnosed Ph+ CML-CP Patients
MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib
MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients
Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall
Best BCR-ABL Ratio Categories for Newly Diagnosed Ph+ CML-CP - Overall
Time to First MMR Among Imatinib or Dasatinib Resistant or Intolerant CML-CP Patients Who Achieved MMR
Time to First MMR Among Newly Diagnosed Ph+ CML-CP Patients Who Achieved MMR
Duration of First MMR Among Patients Who Were Resistant or Intolerant to Either Imatinib or Dasatinib Who Achieved MMR
Duration of First MMR Among Newly Diagnosed Patients Who Achieved MMR
Best Complete Cytogenetic Response (CCyR) Categories in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib - Overall
Best Complete Cytogenetic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients - Overall
Summary of Time to First Complete Cytogenic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients
Kaplan-Meier Estimates of Time to First Complete Cytogenic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients
Kaplan-Meier Estimates of Duration of First Complete Cytogenic Response (CCyR) Among Patients Who Achieved CCyR in Newly Diagnosed Ph+ CML-CP Patients
Best Major Cytogenetic Response (MCyR) Rate by Time Point in Newly Diagnosed Ph+ CML Patients
Summary of Time to First Major Cytogenetic Response (MCyR) Among Patients Who Achieved MCyR in Newly Diagnosed CML-CP Patients
Kaplan-Meier Estimates of Time to First Major Cytogenetic Response (MCyR) in Newly Diagnosed CML-CP Patients
Best Complete Hematological Response (CHR) by Time Point
Summary of Time to First Complete Hematological Response (CHR) Among Patients Who Achieved Confirmed CHR in Newly Diagnosed CML-CP Patients
Kaplan-Meier Estimates of Time to First Complete Hematological Response (CHR) in Newly Diagnosed CML-CP Patients
Time to Disease Progression for Imatinib or Dasatinib Resistant or Intolerant CML-CP Patients - Kaplan-Meier Estimates
Event Free Survival in Imatinib/Dasatinib Resistant/Intolerant CML-CP Patients
Event Free Survival in Newly Diagnosed CML-CP Patients
Overall Survival (OS) in Imatinib/Dasatinib Resistant/Intolerant CML-CP - Kaplan-Meier Estimates
Overall Survival (OS) in Newly Diagnosed CML-CP Patients
Pharmacodynamics (BCR-ABL Transcript Levels Determined With Standard Protocols in Peripheral Blood): Best MMR Status by Cycle
Pharmacokinetics (PK): Steady State Concentration of Nilotinib in Imatinib/Dasatinib Resistant/Intolerant CML-CP Patients
Pharmacokinetics: Steady State Concentration of Nilotinib in Newly Diagnosed CML-CP Patients
Growth Data: Abnormal Height Standard Deviation Scores (SDS) Changes by Cohort
Acceptability (Including Palatability) of Dose Forms Used After First Dose, Cycle 1 and Cycle 12 Study Drug Formulation
Mutational Assessment of BCR-ABL
Long Term Effect of Nilotinib on Bone Metabolism
All Collected Deaths
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- maximum Age
- 17 Years
- minimum Age
- 1 Year
- sex
- ALL
- std Ages
- CHILD
Treatment arms and interventions
- arm Groups
- description
- Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.
- intervention Names
- Drug: nilotinib
- label
- Newly diagnosed and untreated Ph+ CML in first CP
- type
- EXPERIMENTAL
- description
- Resistant or Intolerant to either imatinib or dasatinib
- intervention Names
- Drug: nilotinib
- label
- Resistant/intolerant Ph+ CML in CP
- type
- EXPERIMENTAL
- description
- Resistant or intolerant to either imatinib or dasatinib - at the end no patients were enrolled in this arm.
- intervention Names
- Drug: nilotinib
- label
- Resistant/intolerant Ph+ CML in AP
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Newly diagnosed and untreated Ph+ CML in first CP
- Resistant/intolerant Ph+ CML in AP
- Resistant/intolerant Ph+ CML in CP
- description
- Nilotinib supplied in 50mg, 150mg, and 200mg capsules. It was administered orally at 230mg/m2, twice daily for up to 66 cycles (1 cycle = 28 days). Dose administration was rounded to the nearest 50mg dose (to a maximum dose of 400mg).
- name
- nilotinib
- other Names
- AMN107
- type
- DRUG
Study design
- allocation
- NON_RANDOMIZED
- intervention Model
- SINGLE_GROUP
- masking Info
- masking
- NONE
- primary Purpose
- TREATMENT
Enrollment
- count
- 59
- type
- ACTUAL
Registered outcome plans (not posted results)
- other Outcomes
- description
- The summary of bone age and Dual-energy X-ray absorptiometry (DEXA) by cohort. Alteration of bone biochemical markers of hand and wrist X-Ray evaluation was observed in bone age standard deviation scores (SDS) and for bone mineral density for DEXA before and after treatment with nilotinib.
- measure
- Long Term Effect of Nilotinib on Bone Metabolism
- time Frame
- Cycle 66
- primary Outcomes
- description
- MMR is defined as ≤ 0.1% BCR-ABL/control gene (ABL) % by international scale, or equivalent to ≥ 3 log reduction of BCR-ABL transcript from standardized baseline, measured by RQ-PCR (Real time quantitative polymerase chain reaction). BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. A patient was counted as having MMR at 6 cycles if the patient met the MMR criteria at the Cycle 6 Visit.
- measure
- Rate of Major Molecular Response (MMR) at 6 Cycles for Ph+ CML CP Patients Resistant or Intolerant to Imatinib or Dasatinib
- time Frame
- 6 cycles
- description
- MMR is defined as ≤ 0.1% BCR-ABL/control gene (ABL) % by international scale, or equivalent to ≥ 3 log reduction of BCR-ABL transcript from standardized baseline, measured by RQ-PCR (Real time quantitative polymerase chain reaction). BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. A patient was counted as having MMR by 12 cycles if the patient met the MMR criteria at least once at any time between first study drug intake and Cycle 12 visit included.
- measure
- MMR Rate by 12 Cycles in Newly Diagnosed Ph+ CML-CP Patients
- time Frame
- 12 cycles
- description
- Cytogenetic response is assessed as the percentage of Philadelphia positive (Ph+) metaphases in the bone marrow. Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as CCyR at 12 cycles if the patient met the CCyR criteria at the Cycle 12 Visit.
- measure
- Rate of Complete Cytogenic Response (CCyR) at 12 Cycles in Newly Diagnosed Ph+ CML-CP Patients
- time Frame
- 12 cycles
- secondary Outcomes
- description
- Major molecular response (MMR) was defined as BCR-ABL/ABL % ≤ 0.1% by IS as measured by RQ-PCR, confirmed by duplicate analysis of the same sample.
- measure
- MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib
- time Frame
- By 3, 6, 9 , 12, 24, 36, 48, 66 cycles ( 1 cycle = 28 days)
- description
- Major molecular response (MMR) was defined as BCR-ABL/ABL % ≤ 0.1% by IS as measured by RQ-PCR, confirmed by duplicate analysis of the same sample.
- measure
- MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients
- time Frame
- by 3, 6, 9, 12, 24, 36, 48, 66 cycles (1 cycle = 28 days)
- description
- MMR is defined as ≤ 0.1% BCR-ABL/control gene (ABL) % by international scale, or equivalent to ≥ 3 log reduction of BCR-ABL transcript from standardized baseline, measured by RQ-PCR (Real time quantitative polymerase chain reaction). BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. BCR-ABL ratio by percentage: \> 0.0032 to ≤ 0.01% is equal to a log reduction category of \>= 4 to \<4.5 -log reduction (MR4); BCR-ABL ratio by percentage: \<=0.0032% is equal to a log reduction category of \>= 4.5-log reduction (MMR4.5)
- measure
- Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall
- time Frame
- up to 66 cycles (1 cycle = 28 days)
- description
- MMR is defined as ≤ 0.1% BCR-ABL/control gene (ABL) % by international scale, or equivalent to ≥ 3 log reduction of BCR-ABL transcript from standardized baseline, measured by RQ-PCR (Real time quantitative polymerase chain reaction). BCR-ABL is the fusion gene from breakpoint cluster region and Abelson genes. BCR-ABL ratio by percentage: \> 0.0032 to ≤ 0.01% is equal to a log reduction category of \>= 4 to \<4.5 -log reduction (MR4); BCR-ABL ratio by percentage: \<=0.0032% is equal to a log reduction category of \>= 4.5-log reduction (MMR4.5)
- measure
- Best BCR-ABL Ratio Categories for Newly Diagnosed Ph+ CML-CP - Overall
- time Frame
- up to 66 cycles (1 cycle = 28 days)
- description
- Time from first study drug intake to first MMR amongst imatinib or dasatinib resistant or intolerant patients with CML-CP computed only for patients who achieved MMR.
- measure
- Time to First MMR Among Imatinib or Dasatinib Resistant or Intolerant CML-CP Patients Who Achieved MMR
- time Frame
- From first dosing to the first MMR within 66 cycles period
- description
- Time to MMR is the time from first study drug intake to first major molecular response computed only for participants who achieved MMR.
- measure
- Time to First MMR Among Newly Diagnosed Ph+ CML-CP Patients Who Achieved MMR
- time Frame
- From first dosing to the first MMR within 66 cycles period
- description
- Duration of MMR is defined as the time between the date of the first MMR and the date of confirmed loss of MMR (i.e. the earliest of confirmed loss of MMR, CML-related death or progression to AP or BC). Participants without loss of MMR were censored at the last molecular assessment date.
- measure
- Duration of First MMR Among Patients Who Were Resistant or Intolerant to Either Imatinib or Dasatinib Who Achieved MMR
- time Frame
- from MMR until confirmed loss of MMR (Assessed up to 66 cycles)
- description
- Duration of MMR is defined as the time between the date of the first MMR and the date of confirmed loss of MMR (i.e. the earliest of confirmed loss of MMR, CML-related death or progression to AP or BC). Participants without loss of MMR were censored at the last molecular assessment date.
- measure
- Duration of First MMR Among Newly Diagnosed Patients Who Achieved MMR
- time Frame
- from MMR until confirmed loss of MMR (Assessed up to 66 cycles)es)
- description
- * Complete cytogenetic response (CCyR) - 0% Ph+ metaphases * Partial cytogenetic response (PCyR) - \>0 to 35% Ph+ metaphases * Minor cytogenetic response (mCyR) - \>35 to 65% Ph+ metaphases * Minimal - \>65 to 95% Ph+ metaphases * None - \>95 to 100% Ph+ metaphases * Major cytogenetic response (MCyR) - 0 to 35% Ph+ metaphases. A major response combines both complete and partial responses.
- measure
- Best Complete Cytogenetic Response (CCyR) Categories in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib - Overall
- time Frame
- up to 66 cycles
- description
- Complete cytogenetic response (CCyR) - 0% Ph+ metaphases No response - \>95 to 100% Ph+ metaphases
- measure
- Best Complete Cytogenetic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients - Overall
- time Frame
- up to 66 cycles
- description
- Cytogenetic response is assessed as the percentage of Philadelphia positive (Ph+) metaphases in the bone marrow. Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as having CCyR by 6 cycles (respectively 12 cycles) if the patient met the CCyR criteria at least once at any time between first study drug intake and cycle 6 (cycle 12 respectively) visit included.
- measure
- Summary of Time to First Complete Cytogenic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients
- time Frame
- From first dosing to the first CCyR up to 66 cycles
- description
- Cytogenetic response is assessed as the percentage of Philadelphia positive (Ph+) metaphases in the bone marrow. Complete Cytogenetic Response (CCyR) is defined as 0% of Ph+ metaphases. A patient was counted as having CCyR by 6 cycles (respectively 12 cycles) if the patient met the CCyR criteria at least once at any time between first study drug intake and cycle 6 (cycle 12 respectively) visit included.
- measure
- Kaplan-Meier Estimates of Time to First Complete Cytogenic Response (CCyR) in Newly Diagnosed Ph+ CML-CP Patients
- time Frame
- From first dosing to the first CCyR up to 66 cycles
Full study description
- brief 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).
- detailed Description
- The study was designed as a multi-center, open-label, non-controlled phase II study to assess efficacy, safety and PK parameters of 230 mg/m2 twice daily nilotinib in pediatric patients (1 to \<18 years old). The study population consisted of three cohorts of Ph+ CML pediatric patients: * Cohort 1: Ph+ CML-CP patients resistant or intolerant to either imatinib or dasatinib * Cohort 2: Ph+ CML-AP patients resistant or intolerant to either imatinib or dasatinib * Cohort 3: Newly-diagnosed Ph+ CML-CP patients in first chronic phase A minimum number of 50 pediatric patients (from 1 to \<18 years) were enrolled in the study. Of them, at least 15 patients were Ph+ CML-CP patients resistant or intolerant to either imatinib or dasatinib, and at least 15 were newly-diagnosed Ph+ CML-CP patients in first chronic phase patients. There was no minimum number of patients required for Ph+ CML-AP patients resistant or intolerant to either imatinib or dasatinib. Based on enrollment forecasts as of Jan 2015, and to reflect the agreements with the US FDA and the PDCO, the study remained open for enrollment until the targeted number of 50 patients with at least 15 newly diagnosed Ph+CML patients was achieved or until 31May2015, whichever was later. Patients who completed the study were treated with nilotinib for a total of 66 cycles of 28 days unless the patient prematurely discontinued study treatment. The primary analysis cut-off date was the date when all patients enrolled in the trial either completed their visit for treatment cycle 12 or had discontinued study treatment early (EoT/early discontinuation visit). These analyses were reported in the 12-cycle clinical study report (CSR). A 24-cycle analysis was done when all patients had either completed their 24-cycle treatment visit or had discontinued study treatment early. At trial end, a final comprehensive CSR of all data collected during the trial was produced.
Source references
- references
- citation
- Hijiya N, Maschan A, Rizzari C, Shimada H, Dufour C, Goto H, Kang HJ, Guinipero T, Karakas Z, Bautista F, Ducassou S, Yoo KH, Zwaan CM, Millot F, Patterson BC, Samis J, Izquierdo M, Titorenko K, Li S, Sosothikul D. The long-term efficacy and safety of nilotinib in pediatric patients with CML: a 5-year update of the DIALOG study. Blood Adv. 2023 Dec 12;7(23):7279-7289. doi: 10.1182/bloodadvances.2023010122.
- pmid
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- type
- DERIVED
- citation
- Hijiya N, Maschan A, Rizzari C, Shimada H, Dufour C, Goto H, Kang HJ, Guinipero T, Karakas Z, Bautista F, Ducassou S, Yoo KH, Zwaan CM, Millot F, Patterson B, Samis J, Aimone P, Allepuz A, Titorenko K, Sosothikul D. A phase 2 study of nilotinib in pediatric patients with CML: long-term update on growth retardation and safety. Blood Adv. 2021 Jul 27;5(14):2925-2934. doi: 10.1182/bloodadvances.2020003759.
- pmid
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- type
- DERIVED
- citation
- Hijiya N, Maschan A, Rizzari C, Shimada H, Dufour C, Goto H, Kang HJ, Guinipero T, Karakas Z, Bautista F, Ducassou S, Yoo KH, Zwaan CM, Millot F, Aimone P, Allepuz A, Quenet S, Hourcade-Potelleret F, Hertle S, Sosothikul D. Phase 2 study of nilotinib in pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia. Blood. 2019 Dec 5;134(23):2036-2045. doi: 10.1182/blood.2019000069.
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- type
- DERIVED
Source notices and limitations
Discovery and provenance
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Preserved source evidence · Not medical advice