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.
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
- Conditions the study is for
- Chronic Myeloid Leukemia, Acute Lymphoblastic Leukemia
- 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
Italy3 sites
Novartis Investigative Site
Monza, MB, 20900
Novartis Investigative Site
Padova, PD, 35128
Novartis Investigative Site
Roma, RM, 00161
United Kingdom3 sites
Novartis Investigative Site
Bristol, BS2 8BJ
Novartis Investigative Site
Sutton, Surrey, SM2 5PT
Novartis Investigative Site
West Midlands, Birmingham, B4 6NH
Netherlands2 sites
Novartis Investigative Site
Amsterdam, 1081 HV
Novartis Investigative Site
Rotterdam, 3015 CN
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 group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | 1 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 2 | Experimental | >= 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.
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
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
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
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
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
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
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)
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)
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)
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)
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.
- First posted1 Mar 2010 (estimated)
- Study start14 Apr 2011
- Primary completion1 Jul 2015
- Study completion1 Jul 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
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
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01077544
- Acronym / sponsor ID
- CAMN107A2120
- Keywords
- Chronic Myeloid Leukemia, Acute Lymphoblastic Leukemia, Ph+ CML, Ph+ ALL, pediatric, nilotinib, imatinib, chronic phase
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 14 Apr 2011 (actual)
- Primary completion
- 1 Jul 2015 (actual)
- Study completion
- 1 Jul 2015 (actual)
- First posted
- 1 Mar 2010 (estimated)
- Results
- Posted 27 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Nilotinib1 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. |
| Group 2 | Experimental | Drug: Nilotinib>= 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. |
Who may qualify
- Ages
- 1 year to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NilotinibAlso: AMN107Nilotinib 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. | Drug | Group 1, Group 2 |
Primary outcome
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.
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.
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.
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.
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
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
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.
4 secondary outcomes
Number of Ph+ CML Participants With Confirmed Complete Hematologic Response (CHR)
Time frame: minimum of 12 cycles (28 days per cycle)
Number of Ph+ CML Participants With Cytogenic Response
Time frame: minimum of 12 cycles (28 days per cycle)
Number of Ph+ CML Participants With Major Molecular Response (MMR)
Time frame: minimum of 12 cycles (28 days per cycle)
Efficacy Endpoints for Ph+ ALL Patients
Time frame: minimum of 12 cycles (28 days per cycle)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results for CAMN107A2120 can be found on the Novartis Clinical Trial Results WebsiteLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
12 sites in 4 countries: see every site and its status.
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?
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.