Chronic Myeloid LeukemiaPhase 1CoRNeaNCT02253277
Safety and Tolerability of Combined Treatment With Nilotinib and Ruxolitinib in CML and Ph+ ALL Patients
A Phase 1 study testing Nilotinib and Ruxolitinib in people with Chronic Myeloid Leukemia, run by Novartis Pharmaceuticals at 4 sites in Germany.
Trial summary
In this study it was the rationale to evaluate the safety and tolerability of the combined administration of nilotinib and increasing dose of ruxolitinib in patients with chronic myeloid leukemia and patients with Philadelphia positive acute lymphoblastic leukemia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Myeloid Leukemia
- What is being tested?
- Nilotinib and Ruxolitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 4 sitesGermany
- Study dates
- 18 Feb 2015to 3 Apr 2018
- 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
- Patients of the first stratum must have chronic myeloid leukemia receiving nilotinib first-line therapy or receiving second-line or subsequent-line treatment with nilotinib.
- Patients of the second stratum must have CML in AP/BC or relapsed/refractory Ph+ ALL, or be Ph+ ALL patients with MRD with or without prior nilotinib pretreatment;
- Patients must have adequate end organ function, as defined by:
- Creatinine < 2.0 x upper limit of normal (ULN)
- Total bilirubin < 1.5 x ULN (< 3.0 x ULN if related to disease or polymorphism, such as Mb. Gilbert)
- ALT and AST < 2.5 x ULN (< 5.0 x ULN if related to disease)
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- Serum lipase ≤ 1.5 x ULN
- Alkaline phosphatase ≤ 2.5 x ULN (< 5.0 x ULN if related to disease);
- Patients must have the following electrolyte values within normal limits or corrected to within normal limits with supplements prior to the first dose of study medication:
- Potassium
- Magnesium
- Phosphate
- Total calcium (corrected for serum albumin);
- Female patients of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days before initiation of study drug. All WOCBP must use highly effective contraceptive methods throughout and during 3 months after study;
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1 for patients in CP, ≤ 2 for patients in AP/BC or with relapsed/refractory Ph+ ALL or with Ph+ ALL with MRD;
- Patient has the following laboratory values within 7 days of starting study drug:
- For CML and Ph+ ALL patients: platelet count > 75 x 109/L and ANC > 1.0 x 109/L
Who cannot join
- Patient must not have evidence of active malignancy other than the existing CML or ALL
- Patient must not receive drugs that interfere with coagulation or inhibits platelet function, with the exception of aspirin ≤ 150 mg per day or low molecular weight heparin.
- Patient must not have history of platelet dysfunction, bleeding diathesis, and/or coagulopathy in the 6 months prior to screening;
- Patient must not require treatment with any strong CYP3A4 inducer or inhibitor
- Patient must not have history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes and their excipients;
- Patients must not take other investigational drugs within 28 days prior to screening;
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- Patient must not be pregnant or lactating at screening and/or baseline;
- Patient must not have impaired cardiac functions
- Other protocol-defined inclusion/exclusion criteria may apply
Trial locations and contacts
4 sites in 1 country.
Germany4 sites
Novartis Investigative Site
Berlin, 13353
Novartis Investigative Site
Frankfurt, 60590
Novartis Investigative Site
Jena, 07740
Novartis Investigative Site
Leipzig, 04103
About this study
Official title: A Phase Ib Single-arm, Open-label, Multicenter Study to Assess the Safety and Tolerability of Combined Treatment With Nilotinib 300mg BID and Ruxolitinib Increasing Dose in CML and Ph+ ALL Patients
In this study it was the rationale to evaluate the safety and tolerability of the combined administration of nilotinib and increasing dose of ruxolitinib in patients with chronic myeloid leukemia and patients with Philadelphia positive acute lymphoblastic leukemia.
- Conditions
- Chronic Myeloid Leukemia
- Being tested
- Nilotinib, Ruxolitinib
- Keywords
- CML, Ph+ ALL
- 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
Nilotinib was supplied by Novartis as 150 mg and 200 mg hard gelatin capsules. Nilotinib was not dosed by weight or body surface area. Medication labels were in German and complied with the legal requirements of Germany. They included storage conditions for the drug but no information about the patient. The investigator emphasized compliance and instructed the patient to take nilotinib exactly as prescribed.
RuxolitinibDrug
Ruxolitinib was supplied by Novartis as 5 mg, 15 mg, and 20 mg tablets. Medication labels were in German and complied with the legal requirements of Germany. They included storage conditions for the drug but no information about the patient. The investigator emphasized compliance and instructed the patient to take ruxolitinib exactly as prescribed.
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib and Ruxolitinib | Experimental | The study included two strata, which were to be treated in parallel. The first stratum consisted of CML-patients in CP, which had been on nilotinib treatment before entering the study. These patients did not optimally respond to the previous treatment. The second stratum consisted of patients with CML in AP or BC and patients with relapsed/refractory Ph+ ALL and Ph+ ALL patients with MRD, with or without previous nilotinib treatment. Patients were treated with 300mg nilotinib BID during the escalation phase (12 months) with increasing doses of ruxolitinib. The dose expansion phase (12 months) began following the determination of the MTD of the combination and the decision to explore the cohort for confirmation of RPIID. In this phase, safety and tolerability of the MTD and/or potential RPIID was to be further evaluated, with the purpose of establishing that this dose is suitable for use in this patient group. Receives: Drug: Nilotinib; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurrence of dose limiting toxicities (DLTs)
Occurrence of DLTs during cycle 1
Measured: Baseline, up to day 28 (equals first cycle)
Secondary outcomes (3)
Safety and tolerability profile of nilotinib and ruxolitinib administered in combination
Maximum Tolerated Dose (MTD) and/or Recommended Phase II Dose (RPIID) of ruxolitinib in combination with nilotinib. (timeframe, baseline up to month 12)
Measured: Baseline, up to month 12
Trough levels of nilotinib and ruxolitinib administered in combination
Trough levels will be determined by measuring the minimum plasma concentration (Cmin).
Measured: Baseline, up to month 12
Clinical activity of nilotinib and ruxolitinib administered in combination
Chronic myeloid leukemia in chronic phase: assessment of molecular response: MMR (≤0.1% BCR-ABL) and MR4 (≤0.001% BCR-ABL) at 3, 6, 12 months; Advanced disease: assessment of cytogenetic response will be based on evaluating percentage of Ph+ metaphases
Measured: Baseline and at 3, 6, and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2014 (estimated)
- Study start18 Feb 2015
- Primary completion6 Mar 2018
- Study completion3 Apr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Andreas Hochhaus, Prof. Dr. med., Principal investigator, Jena University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02253277
- Sponsor's protocol ID
- CAMN107YDE19
- Acronym
- CoRNea
- Status last verified
- Apr 2019
- First submitted
- 17 Sep 2014
- Last updated
- 1 May 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Single-arm, Open-label, Multicenter Study to Assess the Safety and Tolerability of Combined Treatment With Nilotinib 300mg BID and Ruxolitinib Increasing Dose in CML and Ph+ ALL Patients
- ClinicalTrials.gov ID
- NCT02253277
- Acronym / sponsor ID
- CoRNea / CAMN107YDE19
- Conditions
- Chronic Myeloid Leukemia
- Keywords
- CML, Ph+ ALL
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 18 Feb 2015 (actual)
- Primary completion
- 6 Mar 2018 (actual)
- Study completion
- 3 Apr 2018 (actual)
- First posted
- 1 Oct 2014 (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.
In this study it was the rationale to evaluate the safety and tolerability of the combined administration of nilotinib and increasing dose of ruxolitinib in patients with chronic myeloid leukemia and patients with Philadelphia positive acute lymphoblastic leukemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib and Ruxolitinib | Experimental | Drug: Nilotinib, Drug: RuxolitinibThe study included two strata, which were to be treated in parallel. The first stratum consisted of CML-patients in CP, which had been on nilotinib treatment before entering the study. These patients did not optimally respond to the previous treatment. The second stratum consisted of patients with CML in AP or BC and patients with relapsed/refractory Ph+ ALL and Ph+ ALL patients with MRD, with or without previous nilotinib treatment. Patients were treated with 300mg nilotinib BID during the escalation phase (12 months) with increasing doses of ruxolitinib. The dose expansion phase (12 months) began following the determination of the MTD of the combination and the decision to explore the cohort for confirmation of RPIID. In this phase, safety and tolerability of the MTD and/or potential RPIID was to be further evaluated, with the purpose of establishing that this dose is suitable for use in this patient group. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Patients of the first stratum must have chronic myeloid leukemia receiving nilotinib first-line therapy or receiving second-line or subsequent-line treatment with nilotinib.
- Patients of the second stratum must have CML in AP/BC or relapsed/refractory Ph+ ALL, or be Ph+ ALL patients with MRD with or without prior nilotinib pretreatment;
- Creatinine < 2.0 x upper limit of normal (ULN)
- Total bilirubin < 1.5 x ULN (< 3.0 x ULN if related to disease or polymorphism, such as Mb. Gilbert)
- ALT and AST < 2.5 x ULN (< 5.0 x ULN if related to disease)
Key exclusion criteria (9 listed)
- Patient must not have evidence of active malignancy other than the existing CML or ALL
- Patient must not receive drugs that interfere with coagulation or inhibits platelet function, with the exception of aspirin ≤ 150 mg per day or low molecular weight heparin.
- Patient must not have history of platelet dysfunction, bleeding diathesis, and/or coagulopathy in the 6 months prior to screening;
- Patient must not require treatment with any strong CYP3A4 inducer or inhibitor
- Patient must not have history of hypersensitivity to any of the study drugs or to drugs of similar chemical classes and their excipients;
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 |
|---|---|---|
| NilotinibNilotinib was supplied by Novartis as 150 mg and 200 mg hard gelatin capsules. Nilotinib was not dosed by weight or body surface area. Medication labels were in German and complied with the legal requirements of Germany. They included storage conditions for the drug but no information about the patient. The investigator emphasized compliance and instructed the patient to take nilotinib exactly as prescribed. | Drug | Nilotinib and Ruxolitinib |
| RuxolitinibRuxolitinib was supplied by Novartis as 5 mg, 15 mg, and 20 mg tablets. Medication labels were in German and complied with the legal requirements of Germany. They included storage conditions for the drug but no information about the patient. The investigator emphasized compliance and instructed the patient to take ruxolitinib exactly as prescribed. | Drug | Nilotinib and Ruxolitinib |
Primary outcome
Occurrence of dose limiting toxicities (DLTs)
Time frame: Baseline, up to day 28 (equals first cycle)
Occurrence of DLTs during cycle 1
3 secondary outcomes
Safety and tolerability profile of nilotinib and ruxolitinib administered in combination
Time frame: Baseline, up to month 12
Trough levels of nilotinib and ruxolitinib administered in combination
Time frame: Baseline, up to month 12
Clinical activity of nilotinib and ruxolitinib administered in combination
Time frame: Baseline and at 3, 6, and 12 months
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 1 May 2019.
- Individual participant dataSharing planned: No
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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.
Andreas Hochhaus, Prof. Dr. med. principal investigator
Jena University Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nilotinib and Ruxolitinib in people with Chronic Myeloid Leukemia, run by Novartis Pharmaceuticals at 4 sites in Germany.
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 17 inclusion and 9 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 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Germany. 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?
Occurrence of dose limiting toxicities (DLTs) (time frame: Baseline, up to day 28 (equals first cycle)). 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 1 May 2019.