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Chronic Myeloid LeukemiaPhase 1NCT01077544

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

A Phase 1 study testing Nilotinib in people with Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Novartis Pharmaceuticals at 12 sites in 4 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 1 year to 17 years
What is being tested?
Nilotinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
15 participants
Where
12 sitesin 4 countries
Study dates
14 Apr 2011to 1 Jul 2015
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 17 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 11Show fewer
  • 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

Trial locations and contacts

12 sites in 4 countries.

12 sites in 4 countries

France4 sites

  • Novartis Investigative Site

    Bordeaux, Aquitaine, 33076

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Paris, 75571

  • Novartis Investigative Site

    Poitiers, 86021

Other trials in France

Italy3 sites

  • Novartis Investigative Site

    Monza, MB, 20900

  • Novartis Investigative Site

    Padova, PD, 35128

  • Novartis Investigative Site

    Roma, RM, 00161

Other trials in Italy

United Kingdom3 sites

  • Novartis Investigative Site

    Bristol, BS2 8BJ

  • Novartis Investigative Site

    Sutton, Surrey, SM2 5PT

  • Novartis Investigative Site

    West Midlands, Birmingham, B4 6NH

Other trials in United Kingdom

Netherlands2 sites

  • Novartis Investigative Site

    Amsterdam, 1081 HV

  • Novartis Investigative Site

    Rotterdam, 3015 CN

Other trials in Netherlands

About this study

Official 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

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.

Being tested
Nilotinib
Keywords
Chronic Myeloid Leukemia, Acute Lymphoblastic Leukemia, Ph+ CML, Ph+ ALL, pediatric, nilotinib, imatinib, chronic phase, accelerated phase, newly diagnosed Ph+ CML, dasatinib
Medical subject headings
Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • NilotinibDrug

    Also called AMN107

    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.

Study groups in NCT01077544
Study groupRoleWhat they receive
Group 1Experimental1 year to < 10 years pediatric patients with newly diagnosed CP-Ph+ CML, or CP or AP-Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or relapsed/refractory Ph+ ALL (acute lymphoblastic leukemia) treated at the proposed dose of 230 mg/m2 bid.
Receives: Drug: Nilotinib
Group 2Experimental>= 10 years to <18 years pediatric patients with newly diagnosed CP-Ph+ CML, or CP or AP-Ph+ CML resistant/intolerant to imatinib and/or dasatinib, or relapsed/refractory Ph+ ALL (acute lymphoblastic leukemia) treated at the proposed dose of 230 mg/m2 bid.
Receives: Drug: Nilotinib

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    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.

    Measured: Cycle 1 Day 1

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

    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.

    Measured: Cycle 1 Day 1

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

    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.

    Measured: Cycle 1 Day 1

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

    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.

    Measured: Cycle 1 Day 1

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

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

    Measured: Cycle 1 Day 8 - Cycle 1 Day 28

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

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

    Measured: Cycle 1 Day 8 - Cycle 1 day 28

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

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

    Measured: Cycle 1 Day 8 - Cycle 1 Day 28

Secondary outcomes (4)

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

    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.

    Measured: minimum of 12 cycles (28 days per cycle)

  2. Number of Ph+ CML Participants With Cytogenic Response

    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.

    Measured: minimum of 12 cycles (28 days per cycle)

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

    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.

    Measured: minimum of 12 cycles (28 days per cycle)

  4. Efficacy Endpoints for Ph+ ALL Patients

    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.

    Measured: minimum of 12 cycles (28 days per cycle)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Mar 2010 (estimated)
  2. Study start14 Apr 2011
  3. Primary completion1 Jul 2015
  4. Study completion1 Jul 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
15 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01077544
Sponsor's protocol ID
CAMN107A2120
Other IDs
2010-018419-14
Status last verified
Oct 2020
First submitted
26 Feb 2010
Last updated
29 Dec 2020
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Nilotinib in people with Chronic Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by Novartis Pharmaceuticals at 12 sites in 4 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in France, Italy, United Kingdom, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 27 Jan 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Summary of Nilotinib Non-compartmental PK Parameters: Cmax (time frame: Cycle 1 Day 1). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01077544.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2020.

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