Chronic Myelogenous LeukemiaPhase 2NCT01274351
Study of Nilotinib as First Line Treatment in Philadelphia Chromosome Positive(Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
A Phase 2 study testing Nilotinib in people with Chronic Myelogenous Leukemia, run by Novartis Pharmaceuticals at 13 sites in Turkey (Türkiye).
Trial summary
The study was a local multicentric, open-label, non-randomized phase II study of nilotinib as a first line treatment in adult patients with newly-diagnosed Philadelphia chromosome-positive (Ph+) and chronic phase myeloid leukemia (CML-CP). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myelogenous 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
- 112 participants
- Where
- 13 sitesTurkey (Türkiye)
- Study dates
- 25 Jan 2011to 1 Aug 2019
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- First cytogenetic diagnosis of CML-CP with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations within 6 months. Standard conventional cytogenetic analysis must be performed.
- Previously untreated for CML, except for hydroxyurea and/or anagrelide (except imatinib treatment for max. 31 days long)
- Adequate end organ function with following laboratory criteria: total bilirubin < 1.5 x upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN); creatinine < 1.5 x upper limit of normal (ULN); serum amylase and lipase ≤ 1.5 x upper limit of normal (ULN); alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN) unless considered tumor related
- Serum potassium, magnesium, and phosphorus levels are equal or above the lower limit of normal prior to the first dose of study medication
Who cannot join
- Treatment with tyrosine kinase inhibitor(s) prior to study (in emergent cases where the patient requires disease management while awaiting study start, commercial supplies of imatinib at any dose may be prescribed to the patient but for no longer than 31 days in duration)
- Known cytopathologically confirmed Central Nervous System CNS infiltration
- Impaired cardiac function
- Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection)
- Acute or chronic liver, pancreatic or severe renal disease considered unrelated to disease
- Patients with another primary malignancy except if the other primary malignancy is neither currently clinically significant or requiring active intervention
Show all 13Show fewer
- History of significant congenital or acquired bleeding disorder unrelated to cancer
- Previous radiotherapy to ≥25% of the bone marrow
- Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of study drug (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection, or gastric bypass surgery)
- Use of therapeutic coumarin derivatives (i.e. warfarin, acenocoumarol, phenprocoumon)
- Patients actively receiving therapy with strong Cytochrome P450 3A4 isoenzyme (CYP3A4) inhibitors (e.g, erythromycin, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir, mibefradil)
- Patients actively receiving therapy with medications that have the potential to prolong the QT interval and the treatment cannot be either discontinued or switched to a different medication prior to starting study drug
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
Turkey (Türkiye)13 sites
Novartis Investigative Site
Adana, 01330
Novartis Investigative Site
Ankara, 06100
Novartis Investigative Site
Bursa, 16059
Novartis Investigative Site
Diyarbakır, 21000
Novartis Investigative Site
Eskişehir, Meselik, 26480
Novartis Investigative Site
Gaziantep, 27310
Novartis Investigative Site
Istanbul, TUR, 34098
Novartis Investigative Site
Istanbul, 34093
Novartis Investigative Site
Izmir, 35040
Novartis Investigative Site
Izmir, 35340
Novartis Investigative Site
Okmeydanı, 34370
Novartis Investigative Site
Talas / Kayseri, 38039
Novartis Investigative Site
Trabzon, 61080
About this study
Official title: A Phase II Multi-center, Open-label, Non-randomized Study of Nilotinib as First Line Treatment in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
The study was a local multicentric, open-label, non-randomized phase II study of nilotinib as a first line treatment in adult patients with newly-diagnosed Philadelphia chromosome-positive (Ph+) and chronic phase myeloid leukemia (CML-CP).
Read the detailed description
This was a multicenter, open-label, single-arm, phase 2 study of nilotinib as a frontline treatment for patients with Ph+ CMLCP. All patients received oral nilotinib 300 mg twice daily for a planned treatment duration of 24 months or until early discontinuation.
The primary efficacy end point was the cumulative rate of Major Molecular Response (MMR) in all participants by 12 months. Secondary efficacy end points included the rate of Complete Cytogenic Response (CCyR) at 6 and 12 months; cumulative rates of MMR up to 24 months; time to and durability of MMR; and cumulative rate of Complete Haematologic Response (CHR) by 12 months.
Patient evaluations, including hematologic assessments, were conducted every 15 days during the first 3 months, monthly until month 12, and then every 3 months until the end of the study (24 months). All efficacy analyses were performed in the intent-to treat population.
- Conditions
- Chronic Myelogenous Leukemia
- Being tested
- Nilotinib
- Keywords
- First line treatment, newly diagnosed, Philadelphia chromosome positive, Chronic Myelogenous Leukemia, Ph+, CML-CP, major molecular response, Social risk
- 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.
NilotinibDrug
Also called Tasigna, AMN107
administered orally at a dose of 300 mg twice daily for 24 months
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Experimental | administered orally at a dose of 300 mg twice daily for 24 months Receives: Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Achieved Major Molecular Response (MMR) During the First 12 Months
Major Molecular Response (MMR) was defined as BCR-ABL1^IS ≤0.1%, on the International Scale [BCR-ABL1IS]) by 12 months. BCR is the Breakpoint Cluster Region gene / BCR gene product and ABL is the Abelson proto-oncogene. BCR-ABL is the Fusion gene from BCR and ABL/Protein product from BCR-ABL. Participants who withdrew prematurely or those who failed to provide data for the study for other reasons were designated as premature withdrawal or inevaluable, respectively, and were included in the ITT analysis as non-responders.
Measured: 12 months
Secondary outcomes (5)
Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months
Major Molecular Response (MMR) was defined as BCR-ABL1^IS ≤0.1%, on the International Scale [BCR-ABL1IS]) by 12 months. BCR is the Breakpoint Cluster Region gene / BCR gene product and ABL is the Abelson proto-oncogene. BCR-ABL is the Fusion gene from BCR and ABL/Protein product from BCR-ABL. Participants who withdrew prematurely or those who failed to provide data for the study for other reasons were designated as premature withdrawal or inevaluable, respectively, and were included in the ITT analysis as non-responders.
Measured: 3, 6, 9, 15, 18, 21 and 24 months
Percentage of Participants With Complete Cytogenetic Response (CCyR) at Month 6 and 12
CCyR rate is identified as the rate of patients who had 0% of Ph+ metaphase.
Measured: Month 6 and 12
Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24
A confirmed complete hematological response (CHR) is defined when all of the following criteria are achieved: WBC <10 x 109/L, thrombocyte <450 x 109/L, myelocyte + metamyelocyte <%5 in blood, no sign of blast and promyelocyte in blood, basophil <%5, and no sign of extramedullary involvement.
Measured: Month 3, 6, 9, 12, 18 and 24
Time to Major Molecular Response (MMR)
Time to MMR is defined as the time period from the date of first dose intake until the first documented MMR.
Measured: 24 months
Duration of Major Molecular Response (MMR)
MMR duration is defined as the time from the date of first documented MMR to the first time of the lost MMR, progression or death.
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2011 (estimated)
- Study start25 Jan 2011
- Primary completion1 Aug 2019
- Study completion1 Aug 2019
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.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 112 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
- NCT01274351
- Sponsor's protocol ID
- CAMN107ETR02
- Status last verified
- Aug 2020
- First submitted
- 4 Jan 2011
- Last updated
- 1 Sep 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
Publications
Saydam G, Haznedaroglu IC, Kaynar L, Yavuz AS, Ali R, Guvenc B, Akay OM, Baslar Z, Ozbek U, Sonmez M, Aydin D, Pehlivan M, Undar B, Dagdas S, Ayyildiz O, Akin G, Dag IM, Ilhan O. Frontline nilotinib treatment in Turkish patients with Philadelphia chromosome-positive chronic Myeloid Leukemia in chronic phase: updated results with 2 years of follow-up. Hematology. 2018 Dec;23(10):771-777. doi: 10.1080/10245332.2018.1498167. Epub 2018 Jul 11.
PubMed 29996726Saydam G, Haznedaroglu IC, Kaynar L, Yavuz AS, Ali R, Guvenc B, Akay OM, Baslar Z, Ozbek U, Sonmez M, Aydin D, Pehlivan M, Undar B, Dagdas S, Ayyildiz O, Akkaynak DZ, Akin G, Ilhan O. Outcomes with frontline nilotinib treatment in Turkish patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Hematology. 2018 Feb 27:1-7. doi: 10.1080/10245332.2018.1444919. Online ahead of print.
PubMed 29486663
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Multi-center, Open-label, Non-randomized Study of Nilotinib as First Line Treatment in Adult Patients With Newly Diagnosed Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia in Chronic Phase (CML-CP)
- ClinicalTrials.gov ID
- NCT01274351
- Acronym / sponsor ID
- CAMN107ETR02
- Conditions
- Chronic Myelogenous Leukemia
- Keywords
- First line treatment, newly diagnosed, Philadelphia chromosome positive, Chronic Myelogenous Leukemia, Ph+, CML-CP, major molecular response, Social risk
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 112 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 25 Jan 2011 (actual)
- Primary completion
- 1 Aug 2019 (actual)
- Study completion
- 1 Aug 2019 (actual)
- First posted
- 11 Jan 2011 (estimated)
- Results
- Posted 1 Sep 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study was a local multicentric, open-label, non-randomized phase II study of nilotinib as a first line treatment in adult patients with newly-diagnosed Philadelphia chromosome-positive (Ph+) and chronic phase myeloid leukemia (CML-CP).
Detailed description
This was a multicenter, open-label, single-arm, phase 2 study of nilotinib as a frontline treatment for patients with Ph+ CMLCP. All patients received oral nilotinib 300 mg twice daily for a planned treatment duration of 24 months or until early discontinuation.
The primary efficacy end point was the cumulative rate of Major Molecular Response (MMR) in all participants by 12 months. Secondary efficacy end points included the rate of Complete Cytogenic Response (CCyR) at 6 and 12 months; cumulative rates of MMR up to 24 months; time to and durability of MMR; and cumulative rate of Complete Haematologic Response (CHR) by 12 months.
Patient evaluations, including hematologic assessments, were conducted every 15 days during the first 3 months, monthly until month 12, and then every 3 months until the end of the study (24 months). All efficacy analyses were performed in the intent-to treat population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib | Experimental | Drug: Nilotinibadministered orally at a dose of 300 mg twice daily for 24 months |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
- First cytogenetic diagnosis of CML-CP with cytogenetic confirmation of Philadelphia chromosome of (9;22) translocations within 6 months. Standard conventional cytogenetic analysis must be performed.
- Previously untreated for CML, except for hydroxyurea and/or anagrelide (except imatinib treatment for max. 31 days long)
- Adequate end organ function with following laboratory criteria: total bilirubin < 1.5 x upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 2.5 x upper limit of normal (ULN); creatinine < 1.5 x upper limit of normal (ULN); serum amylase and lipase ≤ 1.5 x upper limit of normal (ULN); alkaline phosphatase ≤ 2.5 x upper limit of normal (ULN) unless considered tumor related
- Serum potassium, magnesium, and phosphorus levels are equal or above the lower limit of normal prior to the first dose of study medication
Key exclusion criteria (13 listed)
- Treatment with tyrosine kinase inhibitor(s) prior to study (in emergent cases where the patient requires disease management while awaiting study start, commercial supplies of imatinib at any dose may be prescribed to the patient but for no longer than 31 days in duration)
- Known cytopathologically confirmed Central Nervous System CNS infiltration
- Impaired cardiac function
- Severe or uncontrolled medical conditions (i.e. uncontrolled diabetes, active or uncontrolled infection)
- Acute or chronic liver, pancreatic or severe renal disease considered unrelated to disease
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: Tasigna, AMN107administered orally at a dose of 300 mg twice daily for 24 months | Drug | Nilotinib |
Primary outcome
Percentage of Participants Who Achieved Major Molecular Response (MMR) During the First 12 Months
Time frame: 12 months
Major Molecular Response (MMR) was defined as BCR-ABL1^IS ≤0.1%, on the International Scale [BCR-ABL1IS]) by 12 months. BCR is the Breakpoint Cluster Region gene / BCR gene product and ABL is the Abelson proto-oncogene. BCR-ABL is the Fusion gene from BCR and ABL/Protein product from BCR-ABL. Participants who withdrew prematurely or those who failed to provide data for the study for other reasons were designated as premature withdrawal or inevaluable, respectively, and were included in the ITT analysis as non-responders.
5 secondary outcomes
Percentage of Participants Who Achieved Major Molecular Response (MMR) up to 24 Months
Time frame: 3, 6, 9, 15, 18, 21 and 24 months
Percentage of Participants With Complete Cytogenetic Response (CCyR) at Month 6 and 12
Time frame: Month 6 and 12
Percentage of Participants With Complete Hematologic Response (CHR) at Month 3, 6, 9, 12, 18 and 24
Time frame: Month 3, 6, 9, 12, 18 and 24
Time to Major Molecular Response (MMR)
Time frame: 24 months
Duration of Major Molecular Response (MMR)
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29996726Saydam G, Haznedaroglu IC, Kaynar L, Yavuz AS, Ali R, Guvenc B, Akay OM, Baslar Z, Ozbek U, Sonmez M, Aydin D, Pehlivan M, Undar B, Dagdas S, Ayyildiz O, Akin G, Dag IM, Ilhan O. Frontline nilotinib treatment in Turkish patients with Philadelphia chromosome-positive chronic Myeloid Leukemia in chronic phase: updated results with 2 years of follow-up. Hematology. 2018 Dec;23(10):771-777. doi: 10.1080/10245332.2018.1498167. Epub 2018 Jul 11.
- Derived from this study: PubMed 29486663Saydam G, Haznedaroglu IC, Kaynar L, Yavuz AS, Ali R, Guvenc B, Akay OM, Baslar Z, Ozbek U, Sonmez M, Aydin D, Pehlivan M, Undar B, Dagdas S, Ayyildiz O, Akkaynak DZ, Akin G, Ilhan O. Outcomes with frontline nilotinib treatment in Turkish patients with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase. Hematology. 2018 Feb 27:1-7. doi: 10.1080/10245332.2018.1444919. Online ahead of print.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
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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
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nilotinib in people with Chronic Myelogenous Leukemia, run by Novartis Pharmaceuticals at 13 sites in Turkey (Türkiye).
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 5 inclusion and 13 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 1 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in Turkey (Türkiye). 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 1 Sep 2020). 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?
Percentage of Participants Who Achieved Major Molecular Response (MMR) During the First 12 Months (time frame: 12 months). 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 NCT01274351, which also lists 2 linked publications.
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 1 Sep 2020.