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

NCT01844765 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: CAMN107A22032013-000200-41
• Study Type: interventional
• Target: 59
• Locations: 13 countries
• Sites: 36

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).

Conditions

Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia

Keywords

Tasigna; nilotinib treatment; chronic phase; Ph+ CML; accelerated phase; newly diagnosed Ph+ CML; pediatric; 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

Outcome Measures

Primary Outcomes (3)

• Rate of Major Molecular Response (MMR) at 6 Cycles for Ph+ CML CP Patients Resistant or Intolerant to Imatinib or Dasatinib

  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.

  6 cycles

• MMR Rate by 12 Cycles in Newly Diagnosed Ph+ CML-CP Patients

  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.

  12 cycles

• Rate of Complete Cytogenic Response (CCyR) at 12 Cycles in Newly Diagnosed Ph+ CML-CP Patients

  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.

  12 cycles

Secondary Outcomes (30)

• MMR Rate by Time Points in Ph+ CML-CP Patients Resistant or Intolerant to Imatinib or Dasatinib

  By 3, 6, 9 , 12, 24, 36, 48, 66 cycles ( 1 cycle = 28 days)

• MMR Rate by Time Points in Newly Diagnosed Ph+ CML-CP Patients

  by 3, 6, 9, 12, 24, 36, 48, 66 cycles (1 cycle = 28 days)

• Best BCR-ABL Ratio Categories for Resistant/Intolerant Ph+ CML - Overall

  up to 66 cycles (1 cycle = 28 days)

• Best BCR-ABL Ratio Categories for Newly Diagnosed Ph+ CML-CP - Overall

  up to 66 cycles (1 cycle = 28 days)

• Time to First MMR Among Imatinib or Dasatinib Resistant or Intolerant CML-CP Patients Who Achieved MMR

  From first dosing to the first MMR within 66 cycles period

Other Outcomes (1)

• Long Term Effect of Nilotinib on Bone Metabolism

  Cycle 66

Study Arms (3)

Newly diagnosed and untreated Ph+ CML in first CP

EXPERIMENTAL

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

Drug: nilotinib

Resistant/intolerant Ph+ CML in CP

EXPERIMENTAL

Resistant or Intolerant to either imatinib or dasatinib

Drug: nilotinib

Resistant/intolerant Ph+ CML in AP

EXPERIMENTAL

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

Drug: nilotinib

Interventions

nilotinib 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).

Also known as: AMN107

Newly diagnosed and untreated Ph+ CML in first CP; Resistant/intolerant Ph+ CML in AP; Resistant/intolerant Ph+ CML in CP

Eligibility Criteria

• Age: 1 Year - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (36)

Loma Linda University Cancer Center

Loma Linda, California, 92350, United States

Location

Lucile Salter Packard Children's Hospital at Stanford

Palo Alto, California, 94304, United States

Location

Nemours Childrens Hospital

Orlando, Florida, 32827, United States

Location

St. Mary's Hospital

West Palm Beach, Florida, 33407, United States

Location

Johns Hopkins Oncology Center ORA

Baltimore, Maryland, 21231, United States

Location

UNC Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Nationwide Childrens Hospital

Columbus, Ohio, 43205, United States

Location

University of Texas Southwestern Medical Center Oncology

Dallas, Texas, 75235, United States

Location

Cook Children's Medical Center Oncology

Fort Worth, Texas, 76104, United States

Location

Seattle Childrens Hospital

Seattle, Washington, 98105, United States

Location

Novartis Investigative Site

Bordeaux, Aquitaine, 33076, France

Location

Novartis Investigative Site

Lille, 59000, France

Location

Novartis Investigative Site

Paris, 75019, France

Location

Novartis Investigative Site

Poitiers, 86021, France

Location

Novartis Investigative Site

Budapest, 1094, Hungary

Location

Novartis Investigative Site

Genova, GE, 16147, Italy

Location

Novartis Investigative Site

Monza, MB, 20900, Italy

Location

Novartis Investigative Site

Padua, PD, 35128, Italy

Location

Novartis Investigative Site

Torino, TO, 10126, Italy

Location

Novartis Investigative Site

Yokohama, Kanagawa, 232-8555, Japan

Location

Novartis Investigative Site

Sakyo Ku, Kyoto, 606 8507, Japan

Location

Novartis Investigative Site

Shinjuku-ku, Tokyo, 160 8582, Japan

Location

Novartis Investigative Site

Saitama, 330 8777, Japan

Location

Novartis Investigative Site

Shizuoka, 420 8660, Japan

Location

Novartis Investigative Site

Kuala Lumpur, 50589, Malaysia

Location

Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

Location

Novartis Investigative Site

Moscow, 117198, Russia

Location

Novartis Investigative Site

Seoul, 03080, South Korea

Location

Novartis Investigative Site

Seoul, 06351, South Korea

Location

Novartis Investigative Site

Madrid, 28009, Spain

Location

Novartis Investigative Site

Muang, Chiangmai, 50200, Thailand

Location

Novartis Investigative Site

Bangkok, 10330, Thailand

Location

Novartis Investigative Site

Bangkok, 10700, Thailand

Location

Novartis Investigative Site

Istanbul, 34093, Turkey (Türkiye)

Location

Novartis Investigative Site

Sutton, Surrey, SM2 5PT, United Kingdom

Location

Novartis Investigative Site

Bristol, BS2 8BJ, United Kingdom

Location

Related Publications (3)

• 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: 37738125 DERIVED

• 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: 34309636 DERIVED

• 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.

  PMID: 31511239 DERIVED

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia; Bronchiolitis Obliterans Syndrome; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Neoplastic Processes

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Neoplasms by Histologic Type; Neoplasms; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: NovartisPharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: April 29, 2013
• First Posted: May 1, 2013
• Study Start: August 20, 2013
• Primary Completion: June 1, 2016
• Study Completion: August 28, 2020
• Last Updated: April 22, 2021
• Results First Posted: May 21, 2018

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

JP (5); US (10); IT (4); MY (1); NL (1); GB (2); KR (2); ES (1); TU (1); RU (1); TH (3); FR (4); HU (1)