Chronic Myelogenous Leukemia, BCR-ABL1 PositivePhase 1NCT01751425

Ruxolitinib in Treating Participants With Chronic Myeloid Leukemia With Minimal Residual Disease While on Therapy With Tyrosine Kinase Inhibitors

A Phase 1 study testing Dasatinib, Imatinib Mesylate and Nilotinib in people with Chronic Myelogenous Leukemia, BCR-ABL1 Positive and Chronic Myelogenous Leukemia, BCR-ABL1 Positive in Remission, run by M.D. Anderson Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

This phase I/II trial studies the side effects and best dose of ruxolitinib and to see how well it works in participants with chronic myeloid leukemia with minimal residual disease while on therapy with tyrosine kinase inhibitors. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Myelogenous Leukemia, BCR-ABL1 Positive in Remission, Minimal Residual Disease
What is being tested?: Dasatinib, Imatinib Mesylate and Nilotinib
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 8 participants
Where: 1 siteUnited States
Study dates: 24 Jul 2013to 24 Sep 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

Patients with Philadelphia chromosome (Ph)-positive or BCR/ABL-positive CML (as determined by cytogenetics, FISH, or PCR).
Patients must be on continuous TKI therapy for management of their CML. Any commercially available and FDA- approved TKI can be used, i.e., imatinib mesylate (IM), nilotinib (NIL) or dasatinib (DAS). Patients may be receiving TKI at entry in the frontline or salvage setting, including patients currently on imatinib after alpha-interferon failure or on dasatinib or nilotinib after failure to prior therapy including imatinib.
Patients must have received the current TKI for at least 18 months and not have increased their dose in the last 6 months.
For the phase I portion of the study, patients may be included without a CCyR provided they remain in chronic or accelerated phase CML and have at least a complete hematologic response (CHR). For the Phase II portion of the study patients must be in complete cytogenetic remission (CCyR), regardless of the stage of disease they had at the time they started therapy with TKI.
Patients must have detectable BCR-ABL transcript levels meeting at least 1 of the following criteria: Patient has never achieved a major molecular response (MMR, as defined by a BCR-ABL/ABL =< 0.1% in the international scale (currently equivalent to 0.28 in the MD Anderson Cancer Center [MDACC] molecular diagnostic laboratory), and transcript levels have shown in at least 2 consecutive measures separated by at least 1 month to have increased by any value; or achieved a major molecular response which has been lost, with an interim increase in transcript levels by at least one-log, confirmed in two consecutive analyses separated by at least 1 month; or patient has received therapy for at least 2 years \& lacks a sustained major molecular response; or patient has received therapy for at least 5 years and lacks a sustained complete molecular response (CMR, defined as transcript levels still detectable in the MDACC molecular diagnostic laboratory).
Patients must not have had a known interruption of TKI therapy of greater than 21 consecutive days or for a total of 6 weeks in the 6 months prior to enrollment.

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Patients must be able to understand and sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the institutional policies.
Eastern Cooperative Oncology Group (ECOG) performance status =< 2.
Bilirubin < 2 x upper limit of normal (ULN) (unless associated with Gilbert's syndrome).
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) < 2.5 x ULN.
Absolute neutrophil count (ANC) >= 1 x 10(9)/L.
Platelets >= 100 x 10(9)/L.
Serum creatinine < 1.5 mg/dL or creatinine clearance greater or equal than 60 cc/min as defined by the Cockcroft-Gault equation.
Women of childbearing potential should be advised to avoid becoming pregnant while on therapy with ruxolitinib and for 30 days after the last dose and practice effective methods of contraception. Men should be advised not to father a child while receiving treatment with Ruxolitinib and for 30 days after the last dose. Effective methods of contraception for this study include barrier methods (e.g., condoms, diaphragm); spermicidal jelly or foam; oral, depo provera, or injectable hormonal contraceptives; intrauterine devices; tubal ligation; and abstinence.

Who cannot join

For the phase I portion of the study, patients in blast phase. For the phase II portion of the study, patients in accelerated or blast phase.
Patients receiving any other investigational agents.
Patients who are pregnant or breast-feeding.
Patients with clinically significant heart disease (New York Heart Association [NYHA] class III or IV).
Patients with corrected QT (QTc) > 480 msec.
Patients taking a potent CYP3A4 inhibitor that cannot be changed to an alternate drug.

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Known or suspected hypersensitivity to ruxolitinib.
Patients with advanced malignant hepatic tumors.
Patients with known active hepatitis B or C, or human immunodeficiency virus (HIV) infection.
Patients with other medical conditions or concomitant medications that in the opinion of the principal investigator may interfere with the therapeutic treatment.

Trial locations and contacts

1 site in 1 country.

United States1 site

M D Anderson Cancer Center
Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase I-II Study of Ruxolitinib (INCB18424) for Patients With Chronic Myeloid Leukemia (CML) With Minimal Residual Disease While on Therapy With Tyrosine Kinase Inhibitors

Read the detailed description

PRIMARY OBJECTIVES:

To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination of ruxolitinib and a tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML). (Phase I) II. To determine the clinical activity of the combination of ruxolitinib and a TKI in patients with CML in complete cytogenetic remission (CCyR) with minimal residual disease (MRD). (Phase II)

SECONDARY OBJECTIVES:

To determine the clinical activity of the combination of ruxolitinib and a TKI in patients with CML. (Phase I) II. To determine the safety of the combination of ruxolitinib and a TKI in patients with CML in CCyR with minimal residual disease. (Phase II) III. Determine the overall survival, event-free survival and survival free from transformation to accelerated and blast phase. (Phase I and II) IV. Determine the effect of therapy on bone marrow progenitors in clonogenic assays. (Phase I and II) V. Investigate the effect of therapy on molecular responses as assessed by genomic deoxyribonucleic acid (DNA) polymerase chain reaction (PCR). (Phase I and II) VI. Determine the effect of therapy on TKI-resistant quiescent leukemic Philadelphia chromosome (Ph)+ stem cells (CFSEmax/CD34+) by flow cytometric evaluation of activated Crkl and Jak2. (Phase I and II) VII. Assess the effect of therapy on self-renewal and/or survival of leukemic stem cells by fluorescence in situ hybridization (FISH) analysis on colonies. (Phase I and II) VIII. Assess ruxolitinib pharmacokinetics (PK) in preselected time intervals during co-administration of this agent with TKIs. (Phase I and II)

OUTLINE: This is a phase I, dose-escalation study of ruxolitinib followed by a phase II study.

Participants receive commercially available TKIs (imatinib mesylate, nilotinib, or dasatinib) as they had been receiving during the last 6 months and ruxolitinib orally (PO) twice daily (BID). Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, participants are followed up for 30 days.

Conditions: Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Myelogenous Leukemia, BCR-ABL1 Positive in Remission, Minimal Residual Disease, Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia
Being tested: Dasatinib, Imatinib Mesylate, Nilotinib, Ruxolitinib
Medical subject headings: Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Neoplasm, Residual

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DasatinibDrug
Also called BMS-354825, Sprycel
Given PO
Imatinib MesylateDrug
Also called CGP 57148, CGP57148B, Gleevec, Glivec
Given PO
NilotinibDrug
Also called AMN 107 Base Form
Given PO
RuxolitinibDrug
Also called INCB-18424, INCB18424, Oral JAK Inhibitor INCB18424
Given PO

Study groups in NCT01751425
Study group	Role	What they receive
Treatment (TKIs, ruxolitinib)	Experimental	Participants receive commercially available TKIs (imatinib mesylate, nilotinib, or dasatinib) as they had been receiving during the last 6 months and ruxolitinib PO BID. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity. Receives: Drug: Dasatinib; Drug: Imatinib Mesylate; Drug: Nilotinib; Drug: Ruxolitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

Residual disease as measured by polymerase chain reaction (PCR) (Phase II)
It will be determined if the residual disease as measured by PCR can decrease by at least 1 log or become undetectable within 12 months from the start of study therapy. The proportion of patients with response after 12 months of treatment will be determined.
Measured: Up to 7 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Jul 201324 Sep 2019

First posted18 Dec 2012 (estimated)
Study start24 Jul 2013
Primary completion24 Sep 2019
Study completion24 Sep 2019

Why it stopped: Per PI Request. 2) No additional benefit was noted with the addition of Ruxolitinib.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Chronic Myelogenous Leukemia, BCR-ABL1 PositiveStudies of the same condition, open and under way.
More trials run by M.D. Anderson Cancer CenterThe 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
Model description: This study was stopped early and did not go on to phase II.
Masking: None (open label)
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01751425
Sponsor's protocol ID: 2012-0697
Other IDs: NCI-2018-01797, 2012-0697, P30CA016672
Status last verified: May 2025
First submitted: 14 Dec 2012
Last updated: 3 Jun 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 3 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Phase I-II Study of Ruxolitinib (INCB18424) for Patients With Chronic Myeloid Leukemia (CML) With Minimal Residual Disease While on Therapy With Tyrosine Kinase Inhibitors
ClinicalTrials.gov ID: NCT01751425
Acronym / sponsor ID: 2012-0697
Conditions: Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Myelogenous Leukemia, BCR-ABL1 Positive in Remission, Minimal Residual Disease, Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia
Phase: Phase 1
Study type: Interventional
Recruitment status: TerminatedReason stopped: Per PI Request. 2) No additional benefit was noted with the addition of Ruxolitinib.
Enrolment: 8 participants (actual)
Lead sponsor: M.D. Anderson Cancer CenterUniversity, hospital or other
Collaborators: National Cancer Institute (NCI)
Study start: 24 Jul 2013 (actual)
Primary completion: 24 Sep 2019 (actual)
Study completion: 24 Sep 2019 (actual)
First posted: 18 Dec 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.

Detailed description

PRIMARY OBJECTIVES:

To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of the combination of ruxolitinib and a tyrosine kinase inhibitor (TKI) in patients with chronic myeloid leukemia (CML). (Phase I) II. To determine the clinical activity of the combination of ruxolitinib and a TKI in patients with CML in complete cytogenetic remission (CCyR) with minimal residual disease (MRD). (Phase II)

SECONDARY OBJECTIVES:

To determine the clinical activity of the combination of ruxolitinib and a TKI in patients with CML. (Phase I) II. To determine the safety of the combination of ruxolitinib and a TKI in patients with CML in CCyR with minimal residual disease. (Phase II) III. Determine the overall survival, event-free survival and survival free from transformation to accelerated and blast phase. (Phase I and II) IV. Determine the effect of therapy on bone marrow progenitors in clonogenic assays. (Phase I and II) V. Investigate the effect of therapy on molecular responses as assessed by genomic deoxyribonucleic acid (DNA) polymerase chain reaction (PCR). (Phase I and II) VI. Determine the effect of therapy on TKI-resistant quiescent leukemic Philadelphia chromosome (Ph)+ stem cells (CFSEmax/CD34+) by flow cytometric evaluation of activated Crkl and Jak2. (Phase I and II) VII. Assess the effect of therapy on self-renewal and/or survival of leukemic stem cells by fluorescence in situ hybridization (FISH) analysis on colonies. (Phase I and II) VIII. Assess ruxolitinib pharmacokinetics (PK) in preselected time intervals during co-administration of this agent with TKIs. (Phase I and II)

OUTLINE: This is a phase I, dose-escalation study of ruxolitinib followed by a phase II study.

After completion of study treatment, participants are followed up for 30 days.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1
Model description: This study was stopped early and did not go on to phase II.

Arm	Type	Receives
Treatment (TKIs, ruxolitinib)	Experimental	Drug: Dasatinib, Drug: Imatinib Mesylate, Drug: Nilotinib, Drug: RuxolitinibParticipants receive commercially available TKIs (imatinib mesylate, nilotinib, or dasatinib) as they had been receiving during the last 6 months and ruxolitinib PO BID. Courses repeat every 28 days for 2 years in the absence of disease progression or unacceptable toxicity.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (14 listed)

Patients with Philadelphia chromosome (Ph)-positive or BCR/ABL-positive CML (as determined by cytogenetics, FISH, or PCR).
Patients must be on continuous TKI therapy for management of their CML. Any commercially available and FDA- approved TKI can be used, i.e., imatinib mesylate (IM), nilotinib (NIL) or dasatinib (DAS). Patients may be receiving TKI at entry in the frontline or salvage setting, including patients currently on imatinib after alpha-interferon failure or on dasatinib or nilotinib after failure to prior therapy including imatinib.
Patients must have received the current TKI for at least 18 months and not have increased their dose in the last 6 months.
For the phase I portion of the study, patients may be included without a CCyR provided they remain in chronic or accelerated phase CML and have at least a complete hematologic response (CHR). For the Phase II portion of the study patients must be in complete cytogenetic remission (CCyR), regardless of the stage of disease they had at the time they started therapy with TKI.
Patients must have detectable BCR-ABL transcript levels meeting at least 1 of the following criteria: Patient has never achieved a major molecular response (MMR, as defined by a BCR-ABL/ABL =< 0.1% in the international scale (currently equivalent to 0.28 in the MD Anderson Cancer Center [MDACC] molecular diagnostic laboratory), and transcript levels have shown in at least 2 consecutive measures separated by at least 1 month to have increased by any value; or achieved a major molecular response which has been lost, with an interim increase in transcript levels by at least one-log, confirmed in two consecutive analyses separated by at least 1 month; or patient has received therapy for at least 2 years \& lacks a sustained major molecular response; or patient has received therapy for at least 5 years and lacks a sustained complete molecular response (CMR, defined as transcript levels still detectable in the MDACC molecular diagnostic laboratory).

Key exclusion criteria (10 listed)

For the phase I portion of the study, patients in blast phase. For the phase II portion of the study, patients in accelerated or blast phase.
Patients receiving any other investigational agents.
Patients who are pregnant or breast-feeding.
Patients with clinically significant heart disease (New York Heart Association [NYHA] class III or IV).
Patients with corrected QT (QTc) > 480 msec.

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
DasatinibAlso: BMS-354825, SprycelGiven PO	Drug	Treatment (TKIs, ruxolitinib)
Imatinib MesylateAlso: CGP 57148, CGP57148B, Gleevec, GlivecGiven PO	Drug	Treatment (TKIs, ruxolitinib)
NilotinibAlso: AMN 107 Base FormGiven PO	Drug	Treatment (TKIs, ruxolitinib)
RuxolitinibAlso: INCB-18424, INCB18424, Oral JAK Inhibitor INCB18424Given PO	Drug	Treatment (TKIs, ruxolitinib)

Primary outcome

Residual disease as measured by polymerase chain reaction (PCR) (Phase II)
Time frame: Up to 7 years
It will be determined if the residual disease as measured by PCR can decrease by at least 1 log or become undetectable within 12 months from the start of study therapy. The proportion of patients with response after 12 months of treatment will be determined.

Results and safety

The study was stopped early (reason given: Per PI Request. 2) No additional benefit was noted with the addition of Ruxolitinib.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 3 Jun 2025.
MD Anderson Cancer Center 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.

Hagop M. Kantarjian, MD principal investigator

M.D. Anderson Cancer Center

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 14 inclusion and 10 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: stopped early, as of the sponsor's last update on 3 Jun 2025. 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 was stopped early (reason given: Per PI Request. 2) No additional benefit was noted with the addition of Ruxolitinib.). Results are not available in the source record.

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?

Residual disease as measured by polymerase chain reaction (PCR) (Phase II) (time frame: Up to 7 years). 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 NCT01751425.

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 3 Jun 2025.