Skip to main content
OpenTrials
Completed

NCT Number: NCT01077544

A Pharmacokinetic (PK) Study of Nilotinib in Pediatric Patients With Philadelphia Chromosome-positive (Ph+) Chronic Myelogenous Leukemia (CML) or Acute Lymphoblastic Leukemia (ALL)

This study will assess the pharmacokinetics of nilotinib in Ph+ CML pediatric patients that are newly diagnosed or resistant or intolerant to imatinib or dasatinib or refractory or relapsed Ph+ ALL compared to the adult populations. It will also evaluate safety and activity of nilotinib as secondary objectives.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Chronic Myeloid Leukemia Acute Lymphoblastic Leukemia Bone Marrow Diseases Chronic Disease Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid Lymphatic Diseases Lymphoproliferative Disorders Myeloproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Precursor Cell Lymphoblastic Leukemia-Lymphoma

Age range

1 year–17 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Novartis Investigative Site, Bordeaux, Aquitaine, France

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Must have one of the following: newly diagnosed CP Ph+CML, CP or AP resistant/ intolerant to imatinib and/or dasatinib, or Ph+ ALL either relapsed after or refractory to standard therapy
  • adequate renal, hepatic and pancreatic function

Exclusion criteria

  • patients receiving therapy with strong CYP3A4 inhibitors and/or inducers and treatments cannot be stopped or changed to a different medication at least 14 days prior to starting study drug
  • patients receiving therapy with any medications with a known risk or possible risk to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug.
  • gastrointestinal impairment or disease that may interfere with drug absorption
  • liver, pancreatic or severe renal disease unrelated to disease under study
  • impaired cardiac function
  • patients who received dasatinib within 3 days of starting study drug
  • patients who received imatinib within 5 days of starting study drug
  • patients receiving hydroxyurea or corticosteroids that has not been discontinued at least 1 week after initiation of nilotinib
  • patients who received hematopoietic growth factors within 7 days of starting study drug or Pegfilgrastim (Neulasta®) within 14 days of starting study drug
  • patients with Stem Cell Transplant (SCT) or Rescue without TBI: Evidence of active graft vs. host disease and < 3 months since SCT

Other protocol-defined inclusion/exclusion criteria may apply

Treatment and study plan

Nilotinib

Drug

Nilotinib capsules were delivered in bottles with dose strengths of 50mg, 150mg and 200mg.

Patients were administered nilotinib 230 mg/m2 (per BSA) bid, orally, rounded to the nearest 50 mg (max single dose 400 mg) for 28 days (1 cycle) for up to 12 cycles prior to protocol amendment 3 and up to 24 cycles post amendment 3. Capsules were to be swallowed whole with water. Apple sauce (puréed apple) may have been used as a vehicle for dosing where capsules were not able to be swallowed whole with water.

Other names: AMN107

Primary outcomes

  1. Summary of Nilotinib Non-compartmental PK Parameters: Cmax

    Time frame: Cycle 1 Day 1

    The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

  2. Summary of Nilotinib Non-compartmental PK Parameters: Tmax

    Time frame: Cycle 1 Day 1

    The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

  3. Summary of Nilotinib Non-compartmental PK Parameters: AUClast (Last = 24h)

    Time frame: Cycle 1 Day 1

    The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

  4. Summary of Nilotinib Non-compartmental PK Parameters: AUC0-12h

    Time frame: Cycle 1 Day 1

    The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose on Cycle 1 Day 1.

  5. Summary of Nilotinib Steady-state PK Parameters: AUCss

    Time frame: Cycle 1 Day 8 - Cycle 1 Day 28

    The steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses

  6. Summary of Nilotinib Steady-state PK Parameters: CLF (Body Surface Area (BSA) Adjusted)

    Time frame: Cycle 1 Day 8 - Cycle 1 day 28

    The steady-state PK profiles of nilotinib in pediatric patients were estimated using trough sampling following multiple 230 mg/m2 bid doses

  7. Summary of Nilotinib Steady-state PK Parameters: Cmin

    Time frame: Cycle 1 Day 8 - Cycle 1 Day 28

    The full PK profiles of nilotinib in pediatric patients were assessed using serial sampling following a single 230 mg/m2 dose.

Secondary outcomes

  1. Number of Ph+ CML Participants With Confirmed Complete Hematologic Response (CHR)

    Time frame: minimum of 12 cycles (28 days per cycle)

    A confirmed complete hematological response (CHR) is defined when all of the following criteria are achieved at two consecutive assessments, at least 4 weeks apart: white blood cell (WBC) count < 10 × 109/L; platelet < 450 × 109/L; basophils < 5%; no blasts and promyelocytes in peripheral blood (PB); myelocytes + metamyelocytes < 5% in PB; and no extramedullary involvement. The information used for hematological assessment was to be obtained from the laboratory and extramedullary data, all merged by patient and date.

  2. Number of Ph+ CML Participants With Cytogenic Response

    Time frame: minimum of 12 cycles (28 days per cycle)

    Cytogenetic response was initially assessed as the percentage of Ph+ metaphases in the bone marrow (BM) and performed within 21 days prior to study entry. A major cytogenetic response (0% to 35% Ph+ metaphases test positive for the Philadelphia chromosome) combines both complete cytogenetic (CCyR) and partial cytogenetic response (PCyR). CCyR implies 0% Ph+ metaphases in the BM, PCyR is > 0% to 35%, minor cytogenetic response (mCyR) is > 35% to 65%, minimal response is > 65% to 95% and no response is > 95% Ph+ metaphases in the BM.

  3. Number of Ph+ CML Participants With Major Molecular Response (MMR)

    Time frame: minimum of 12 cycles (28 days per cycle)

    The bcr-abl gene fusion encodes for a BCR-ABL fusion protein. Depending on the precise location of the fusion, the molecular weight of this protein can range from 185 to 210 kDa. Consequently BCR-ABL is referred to as p185 or p210 transcript. For the patients expressing the major BCR-ABL transcript p210, molecular response was defined and reported as the percent ratio of BCR-ABL transcripts/control gene transcripts converted to a reference standard according to the International Scale (IS). A major molecular response (MMR) is defined as a BCR-ABL/control gene ratio ≤ 0.1% (equal to a 3 log reduction in BCR-ABL transcripts) on the IS. In this study, the control gene was abl.

  4. Efficacy Endpoints for Ph+ ALL Patients

    Time frame: minimum of 12 cycles (28 days per cycle)

    Best Response in Ph+ ALL patients was defined as either Complete Remission (CR) with platelet recovery, Complete Remission (CR) with incomplete platelet recovery, Partial Remission (PR) or Stable disease. Stable disease was defined is defined as failure to qualify for either CR, PR, or progressive disease.

Sponsors and collaborators

Lead sponsor

Novartis Pharmaceuticals

Industry

Registry information

Official study title

A Multi-center, Open-label, Pharmacokinetic Study of Oral Nilotinib in Pediatric Patients With Newly Diagnosed Chronic Phase (CP) Ph+ CML, With CP or Accelerated Phase (AP) Ph+ CML Resistant/Intolerant to Imatinib and/or Dasatinib, or With Refractory/Relapsed Ph+ ALL

Important dates

Study start
2011
Primary completion
2015
Study completion
2015
First posted
Mar 1, 2010
Registry last updated
Dec 29, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.