Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

NCT ID: NCT01844765

Last Updated: 2021-04-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-20
• Study Completion Date: 2020-08-28

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.

Conditions

Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Newly diagnosed and untreated Ph+ CML in first CP

Diagnosis within 6 months of date of first cytogenetic analysis confirming Philadelphia chromosome with (9;22) translocation by standard conventional cytogenetic analysis.

Group Type: EXPERIMENTAL

nilotinib

Intervention Type: DRUG

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).

Resistant/intolerant Ph+ CML in CP

Resistant or Intolerant to either imatinib or dasatinib

Group Type: EXPERIMENTAL

nilotinib

Intervention Type: DRUG

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).

Resistant/intolerant Ph+ CML in AP

Resistant or intolerant to either imatinib or dasatinib - at the end no patients were enrolled in this arm.

Group Type: EXPERIMENTAL

nilotinib

Intervention Type: DRUG

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).

Interventions

nilotinib

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).

Intervention Type: DRUG

Other Intervention Names

AMN107

Eligibility Criteria

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

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

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Loma Linda University Cancer Center

Loma Linda, California, United States

Lucile Salter Packard Children's Hospital at Stanford

Palo Alto, California, United States

Nemours Childrens Hospital

Orlando, Florida, United States

St. Mary's Hospital

West Palm Beach, Florida, United States

Johns Hopkins Oncology Center ORA

Baltimore, Maryland, United States

UNC Chapel Hill

Chapel Hill, North Carolina, United States

Nationwide Childrens Hospital

Columbus, Ohio, United States

University of Texas Southwestern Medical Center Oncology

Dallas, Texas, United States

Cook Children's Medical Center Oncology

Fort Worth, Texas, United States

Seattle Childrens Hospital

Seattle, Washington, United States

Novartis Investigative Site

Bordeaux, Aquitaine, France

Novartis Investigative Site

Lille, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Poitiers, , France

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Genova, GE, Italy

Novartis Investigative Site

Monza, MB, Italy

Novartis Investigative Site

Padua, PD, Italy

Novartis Investigative Site

Torino, TO, Italy

Novartis Investigative Site

Yokohama, Kanagawa, Japan

Novartis Investigative Site

Sakyo Ku, Kyoto, Japan

Novartis Investigative Site

Shinjuku-ku, Tokyo, Japan

Novartis Investigative Site

Saitama, , Japan

Novartis Investigative Site

Shizuoka, , Japan

Novartis Investigative Site

Kuala Lumpur, , Malaysia

Novartis Investigative Site

Rotterdam, , Netherlands

Novartis Investigative Site

Moscow, , Russia

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Muang, Chiangmai, Thailand

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Bangkok, , Thailand

Novartis Investigative Site

Istanbul, , Turkey (Türkiye)

Novartis Investigative Site

Sutton, Surrey, United Kingdom

Novartis Investigative Site

Bristol, , United Kingdom

Countries

United States; France; Hungary; Italy; Japan; Malaysia; Netherlands; Russia; South Korea; Spain; Thailand; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 37738125 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34309636 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31511239 (View on PubMed)

Other Identifiers

2013-000200-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CAMN107A2203

Identifier Type: -

Identifier Source: org_study_id