Chronic Phase Chronic Myeloid LeukemiaPhase 1NCT01702064
Ruxolitinib in Combination With Nilotinib in Chronic Myeloid Leukemia (CML) Patients
A Phase 1 study testing Nilotinib and Ruxolitinib in people with Chronic Phase Chronic Myeloid Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
This study is designed to determine the maximal tolerated dose of Ruxolitinib in combination with nilotinib in patients with chronic myeloid leukemia (CML). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Phase 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
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Feb 2013to 9 Jan 2019
- 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
- Must have chronic phase chronic myeloid leukemia (CML). They must also be under treatment with nilotinib as either first, second, or third-line therapy.
- Must have a complete cytogenetic response (CCyR) OR must have been on nilotinib for a minimum of 6 months.
- Must not have undergone treatment for any other form of cancer (aside from non-melanoma skin cancer) in the past 5 years.
- 18 years of age or older and must be able to speak and read English or Spanish.
- Able to provide informed consent.
- Prior therapy with a tyrosine kinase inhibitor (TKI) other than nilotinib is allowable, however, nilotinib must be the current therapy. All participants must be under the care of a Moffitt Cancer Center physician, and enrollment is expected to be complete within 6 months.
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- Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Karnofsky ≥60%.
- Must have normal organ and marrow function as defined in study protocol.
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of Ruxolitinib and nilotinib administration. Women of child-bearing age will be required to have a negative pregnancy test within 14 days of enrolling in this study.
- Ability to understand and the willingness to sign a written informed consent document
- B-HCG will be performed on all women of child-bearing potential as screening prior to enrollment on this trial. STAT3 levels in the bone marrow will also be measured prior to enrollment.
Who cannot join
- Patients who are in accelerated phase or blast phase CML.
- May not be receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in the study.
- Known history of a prolonged QT interval (QTc >480).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study. Women who are breast feeding their infants should discontinue this practice if the mother is treated with ruxolitinib.
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- Currently receiving any drugs considered to be strong CYP3A4 inducers or inhibitors which cannot be discontinued or changed to an alternative drug prior to enrolling on the trial.
- HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study.
- Patients receiving nilotinib 200 mg by mouth, twice a day (PO BID) or a lower dose are not eligible.
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase I Study of Ruxolitinib in Combination With Nilotinib in CML Patients With Evidence of Molecular Disease
This study is designed to determine the maximal tolerated dose of Ruxolitinib in combination with nilotinib in patients with chronic myeloid leukemia (CML).
- Conditions
- Chronic Phase Chronic Myeloid Leukemia
- Being tested
- Nilotinib, Ruxolitinib
- Keywords
- CML, CP-CML, Chronic Phase-CML (CP-CML), chronic myeloid leukemia
- Medical subject headings
- Leukemia, Myeloid, Chronic-Phase, 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, BCR-ABL kinase inhibitor
Participants will remain on the same dose of nilotinib they have been receiving prior to enrollment on the trial. This will range from 300 mg PO BID to 400 mg PO BID.
Dose modifications will not occur, as the purpose of this study is to determine the maximum tolerated dose of ruxolitinib, based on the number of dose.
RuxolitinibDrug
Also called INCB018424
Dose escalation will follow a 3+3 study design. Dose modifications will not occur, as the purpose of this study is to determine the maximum tolerated dose, based on the number of dose limiting toxicities seen at a specific dose.
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib with Ruxolitinib | Experimental | The starting dose of ruxolitinib will be 5mg by mouth (PO) twice a day (BID) and will increase by 5 mg increments in each cohort, to a maximum dose of 15 mg PO BID. Nilotinib will be given at a dose ranging from 300 mg PO BID to 400 mg PO BID, depending on the participant's dose prior to enrollment on the trial.
Dose Level 1: Ruxolitinib 5 mg twice a day (BID); Nilotinib 300 mg or 400 mg BID.
Dose Level 2: Ruxolitinib 10 mg BID; Nilotinib 300 mg or 400 mg BID.
Dose Level 3: Ruxolitinib 15 mg BID; Nilotinib 300 mg or 400 mg BID. Receives: Drug: Nilotinib; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Maximum Tolerated Dose (MTD)
Maximum tolerated dose (MTD) of ruxolitinib with nilotinib. Dose escalation will follow a 3+3 study design. If 2 or more participants within a cohort experience a dose limiting toxicity (DLT), then the MTD will have been exceeded and the preceding dose level will be evaluated as the MTD. A minimum of 6 participants must be evaluated at the dose level in order for it to be declared as the MTD.
Dose limiting toxicity is defined as:
- Any non-hematological toxicity ≥ grade three, excluding any untreated nausea, vomiting, diarrhea or fatigue that occurs during the first 56 days of therapy.
- Grade three thrombocytopenia with active bleeding or grade four thrombocytopenia or febrile neutropenia (ANC <500 cells/µL and fever > 101.0 F (38.5C)).
- Any treatment related grade five toxicity (i.e., death).
Measured: Average of 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2012 (estimated)
- Study start21 Feb 2013
- Primary completion17 Oct 2016
- Study completion9 Jan 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Phase Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation
- Responsible party
- Sponsor
- Investigators
- Kendra Sweet, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01702064
- Sponsor's protocol ID
- MCC-17114
- Status last verified
- Jan 2021
- First submitted
- 3 Oct 2012
- Last updated
- 5 Jan 2021
- Results posted
- No
- Data monitoring committee
- No
Publications
Sweet K, Hazlehurst L, Sahakian E, Powers J, Nodzon L, Kayali F, Hyland K, Nelson A, Pinilla-Ibarz J. A phase I clinical trial of ruxolitinib in combination with nilotinib in chronic myeloid leukemia patients with molecular evidence of disease. Leuk Res. 2018 Nov;74:89-96. doi: 10.1016/j.leukres.2018.10.002. Epub 2018 Oct 9.
PubMed 30340199
Study at a glance
From the registry record, last updated by the sponsor on 5 Jan 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of Ruxolitinib in Combination With Nilotinib in CML Patients With Evidence of Molecular Disease
- ClinicalTrials.gov ID
- NCT01702064
- Acronym / sponsor ID
- MCC-17114
- Conditions
- Chronic Phase Chronic Myeloid Leukemia
- Keywords
- CML, CP-CML, Chronic Phase-CML (CP-CML), chronic myeloid leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Incyte Corporation
- Study start
- 21 Feb 2013 (actual)
- Primary completion
- 17 Oct 2016 (actual)
- Study completion
- 9 Jan 2019 (actual)
- First posted
- 5 Oct 2012 (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.
This study is designed to determine the maximal tolerated dose of Ruxolitinib in combination with nilotinib in patients with chronic myeloid leukemia (CML).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib with Ruxolitinib | Experimental | Drug: Nilotinib, Drug: RuxolitinibThe starting dose of ruxolitinib will be 5mg by mouth (PO) twice a day (BID) and will increase by 5 mg increments in each cohort, to a maximum dose of 15 mg PO BID. Nilotinib will be given at a dose ranging from 300 mg PO BID to 400 mg PO BID, depending on the participant's dose prior to enrollment on the trial. Dose Level 1: Ruxolitinib 5 mg twice a day (BID); Nilotinib 300 mg or 400 mg BID. Dose Level 2: Ruxolitinib 10 mg BID; Nilotinib 300 mg or 400 mg BID. Dose Level 3: Ruxolitinib 15 mg BID; Nilotinib 300 mg or 400 mg BID. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Must have chronic phase chronic myeloid leukemia (CML). They must also be under treatment with nilotinib as either first, second, or third-line therapy.
- Must have a complete cytogenetic response (CCyR) OR must have been on nilotinib for a minimum of 6 months.
- Must not have undergone treatment for any other form of cancer (aside from non-melanoma skin cancer) in the past 5 years.
- 18 years of age or older and must be able to speak and read English or Spanish.
- Able to provide informed consent.
Key exclusion criteria (9 listed)
- Patients who are in accelerated phase or blast phase CML.
- May not be receiving any other investigational agents.
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to ruxolitinib or other agents used in the study.
- Known history of a prolonged QT interval (QTc >480).
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
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, BCR-ABL kinase inhibitorParticipants will remain on the same dose of nilotinib they have been receiving prior to enrollment on the trial. This will range from 300 mg PO BID to 400 mg PO BID. Dose modifications will not occur, as the purpose of this study is to determine the maximum tolerated dose of ruxolitinib, based on the number of dose. | Drug | Nilotinib with Ruxolitinib |
| RuxolitinibAlso: INCB018424Dose escalation will follow a 3+3 study design. Dose modifications will not occur, as the purpose of this study is to determine the maximum tolerated dose, based on the number of dose limiting toxicities seen at a specific dose. | Drug | Nilotinib with Ruxolitinib |
Primary outcome
Phase I: Maximum Tolerated Dose (MTD)
Time frame: Average of 6 months
Maximum tolerated dose (MTD) of ruxolitinib with nilotinib. Dose escalation will follow a 3+3 study design. If 2 or more participants within a cohort experience a dose limiting toxicity (DLT), then the MTD will have been exceeded and the preceding dose level will be evaluated as the MTD. A minimum of 6 participants must be evaluated at the dose level in order for it to be declared as the MTD. Dose limiting toxicity is defined as: * Any non-hematological toxicity ≥ grade three, excluding any untreated nausea, vomiting, diarrhea or fatigue that occurs during the first 56 days of therapy. * Grade three thrombocytopenia with active bleeding or grade four thrombocytopenia or febrile neutropenia (ANC <500 cells/µL and fever > 101.0 F (38.5C)). * Any treatment related grade five toxicity (i.e., death).
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 5 Jan 2021.
- Derived from this study: PubMed 30340199Sweet K, Hazlehurst L, Sahakian E, Powers J, Nodzon L, Kayali F, Hyland K, Nelson A, Pinilla-Ibarz J. A phase I clinical trial of ruxolitinib in combination with nilotinib in chronic myeloid leukemia patients with molecular evidence of disease. Leuk Res. 2018 Nov;74:89-96. doi: 10.1016/j.leukres.2018.10.002. Epub 2018 Oct 9.
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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.
Kendra Sweet, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
1 site 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 Phase Chronic Myeloid Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
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 11 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 5 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
Phase I: Maximum Tolerated Dose (MTD) (time frame: Average of 6 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 NCT01702064, which also lists 1 linked publication.
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 5 Jan 2021.