Philadelphia Chromosome Positive Chronic Myelogenous LeukemiaPhase 1NCT01456676
Nilotinib and LDE225 in the Treatment of Chronic or Accelerated Phase Myeloid Leukemia in Patients Who Developed Resistance to Prior Therapy
A Phase 1 study testing Nilotinib + LDE225 in people with Philadelphia Chromosome Positive Chronic Myelogenous Leukemia, run by Novartis Pharmaceuticals at 7 sites in 5 countries.
Trial summary
The purpose of this study is to determine the feasibility of administering the combination of nilotinib and LDE225 to patients with chronic or accelerated phase of chronic myeloid leukemia and to establish the maximum tolerated dose (MTD) and/or recommended Phase II dose level (RP2D) of LDE225 in combination with… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
- What is being tested?
- Nilotinib + LDE225
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 7 sitesin 5 countries
- Study dates
- Jan 2012to Feb 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Philadelphia chromosome positive (Ph+) CML in chronic phase (CP) or accelerated phase (AP)with resistance to at least one prior BCR-ABL targeting TKI
- Documented chronic phase CML
- Adequate end organ function
- Female patients of childbearing potential must have a negative serum pregnancy test and must be using highly effective methods of contraception. Male patients with female partners of child-bearing potential must use condoms.
Who cannot join
- Impaired cardiac function
- Severe and/or uncontrolled concurrent disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
- History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
- Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to entering the study
- Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug.
- Previously documented BCR-ABL Y253H, E255K/V, T315I or F359C/V mutation
- Other protocol-defined inclusion/exclusion criteria may apply.
Trial locations and contacts
7 sites in 5 countries.
7 sites in 5 countries
Germany2 sites
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Ulm, 89081
Spain2 sites
Novartis Investigative Site
Madrid, 28006
Novartis Investigative Site
Pamplona, Navarre, 31008
About this study
Official title: A Single-arm Dose-finding Phase Ib Multicenter Study of the Oral Smoothened Antagonist LDE225 in Combination With Nilotinib in Chronic or Accelerated Phase of Chronic Myeloid Leukemia Patients Who Have Failed Prior Therapy With Other BCR-ABL Tyrosine-kinase Inhibitors
The purpose of this study is to determine the feasibility of administering the combination of nilotinib and LDE225 to patients with chronic or accelerated phase of chronic myeloid leukemia and to establish the maximum tolerated dose (MTD) and/or recommended Phase II dose level (RP2D) of LDE225 in combination with nilotinib.
- Being tested
- Nilotinib + LDE225
- Keywords
- LDE225, nilotinib, Chronic myeloid leukemia, CML, Philadelphia positive, Ph+, resistant, Resistant Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP)
- Medical subject headings
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nilotinib + LDE225Drug
Nilotinib is an aminopyrimidine ATP-competitive inhibitor of the protein tyrosine kinaseactivity of BCR-ABL.
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib + LDE225 | Experimental | The planned dose of nilotinib 400 mg b.i.d (twice a day) was selected for the combination as this is the dose approved for the treatment of the patient population that will be included in the present study. The starting dose for LDE225 chosen for the current study is 400 mg once daily(q.d.). The maximum dose of LDE225 that will be tested in combination with nilotinib is 800 mg once dail.y Receives: Drug: Nilotinib + LDE225 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy
Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225
Measured: 56 days (2 treatment cycles at 28 days each)
Secondary outcomes (6)
No of participants with Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms
Assessment of the safety and tolerability profile of nilotinib in combination with LDE225
Measured: 336 days (12 treatment cycles)
Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC)
Assessment of the PK characteristics of nilotinib administered in combination with LDE225
Measured: 50 days
Major molecular response (MMR) rates at 3, 6 and 12 months
Determination of the kinetics of major molecular response
Measured: 336 days (12 treatment cycles)
Complete molecular response (CMR) rates at 3, 6 and 12 months
Determination of the kinetics of complete molecular response
Measured: 336 days (12 treatment cycles)
Major cytogenic response (MCyR) rates by 3, 6 and 12 months
Determination of major cytogenetic response rates
Measured: 336 days (12 treatment cycles)
Complete cytogenic response (CCyR) rates by 3, 6 and 12 months
Determination of complete cytogenetic response rates
Measured: 336 days (12 treatment cycles)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Oct 2011 (estimated)
- Study startJan 2012
- Primary completionFeb 2014
- Study completionFeb 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Philadelphia Chromosome Positive Chronic Myelogenous 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 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
- NCT01456676
- Sponsor's protocol ID
- CAMN107Y2101
- Other IDs
- 2011-000282-12
- Status last verified
- Sep 2016
- First submitted
- 14 Oct 2011
- Last updated
- 9 Dec 2020
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-arm Dose-finding Phase Ib Multicenter Study of the Oral Smoothened Antagonist LDE225 in Combination With Nilotinib in Chronic or Accelerated Phase of Chronic Myeloid Leukemia Patients Who Have Failed Prior Therapy With Other BCR-ABL Tyrosine-kinase Inhibitors
- ClinicalTrials.gov ID
- NCT01456676
- Acronym / sponsor ID
- CAMN107Y2101
- Keywords
- LDE225, nilotinib, Chronic myeloid leukemia, CML, Philadelphia positive, Ph+, resistant, Resistant Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Jan 2012
- Primary completion
- Feb 2014 (actual)
- Study completion
- Feb 2014 (actual)
- First posted
- 21 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the feasibility of administering the combination of nilotinib and LDE225 to patients with chronic or accelerated phase of chronic myeloid leukemia and to establish the maximum tolerated dose (MTD) and/or recommended Phase II dose level (RP2D) of LDE225 in combination with nilotinib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib + LDE225 | Experimental | Drug: Nilotinib + LDE225The planned dose of nilotinib 400 mg b.i.d (twice a day) was selected for the combination as this is the dose approved for the treatment of the patient population that will be included in the present study. The starting dose for LDE225 chosen for the current study is 400 mg once daily(q.d.). The maximum dose of LDE225 that will be tested in combination with nilotinib is 800 mg once dail.y |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Philadelphia chromosome positive (Ph+) CML in chronic phase (CP) or accelerated phase (AP)with resistance to at least one prior BCR-ABL targeting TKI
- Documented chronic phase CML
- Adequate end organ function
- Female patients of childbearing potential must have a negative serum pregnancy test and must be using highly effective methods of contraception. Male patients with female partners of child-bearing potential must use condoms.
Key exclusion criteria (7 listed)
- Impaired cardiac function
- Severe and/or uncontrolled concurrent disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol
- History of acute pancreatitis within 1 year of study entry or past medical history of chronic pancreatitis
- Patients actively receiving therapy with strong CYP3A4 inhibitors and/or inducers, and the treatment cannot be either discontinued or switched to a different medication prior to entering the study
- Patients who are currently receiving treatment with any medications that have the potential to prolong the QT interval and the treatment cannot be either safely discontinued or switched to a different medication prior to starting study drug.
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 |
|---|---|---|
| Nilotinib + LDE225Nilotinib is an aminopyrimidine ATP-competitive inhibitor of the protein tyrosine kinaseactivity of BCR-ABL. | Drug | Nilotinib + LDE225 |
Primary outcome
Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy
Time frame: 56 days (2 treatment cycles at 28 days each)
Determination of the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of nilotinib in combination with LDE225
6 secondary outcomes
No of participants with Adverse drug reactions and serious adverse drug reactions, changes in hematology and blood chemistry values, assessments of physical examinations, vital signs and electrocardiograms
Time frame: 336 days (12 treatment cycles)
Plasma concentration and basic pharmacokinetics (PK) parameters (as Cmax, Tmax, AUC)
Time frame: 50 days
Major molecular response (MMR) rates at 3, 6 and 12 months
Time frame: 336 days (12 treatment cycles)
Complete molecular response (CMR) rates at 3, 6 and 12 months
Time frame: 336 days (12 treatment cycles)
Major cytogenic response (MCyR) rates by 3, 6 and 12 months
Time frame: 336 days (12 treatment cycles)
Complete cytogenic response (CCyR) rates by 3, 6 and 12 months
Time frame: 336 days (12 treatment cycles)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2020.
- Reuslts for CAMN107Y2101 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
7 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nilotinib + LDE225 in people with Philadelphia Chromosome Positive Chronic Myelogenous Leukemia, run by Novartis Pharmaceuticals at 7 sites in 5 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 4 inclusion and 7 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 9 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 7 sites in Germany, Spain, Canada, France, Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence rate and category of dose limiting toxicities (DLTs) during the first two cycles of therapy (time frame: 56 days (2 treatment cycles at 28 days each)). 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 9 Dec 2020.