Myelomonocytic LeukemiaPhase 1/2NCT01776723
A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Ruxolitinib
A Phase 1/2 study testing Ruxolitinib in people with Myelomonocytic Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute at 6 sites in United States.
Trial summary
The purpose of this study is to find out if treating Chronic Myelomonocytic Leukemia (CMML) with a study drug [ruxolitinib] can improve outcomes of patients with CMML. The first step of the study is to learn the dose of ruxolitinib that is tolerable (bearable). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelomonocytic Leukemia
- What is being tested?
- Ruxolitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 6 sitesUnited States
- Study dates
- 20 Feb 2013to 10 May 2022
- Phase
- Phase 1/2
- 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
- Confirmed diagnosis of CMML using the World Health Organization (WHO) classification
- Age >18 years at the time of obtaining informed consent
- Must be able to adhere to the study visit schedule and other protocol requirements
- Must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for histopathological analysis and standard cytogenetic analysis during the screening procedure
- An Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1, or 2
- Women of childbearing potential must have a negative pregnancy test at time of screening and baseline visits and agree to use two reliable forms of contraception simultaneously or to practice complete abstinence from heterosexual intercourse 1) for at least 28 days before starting study drug; 2) while participating in the study; and 3) for at least 28 days after discontinuation from the study.
- Must understand and voluntarily sign an informed consent form
- Must have a life expectancy of greater than 3 months at time of screening
Who cannot join
- Platelet count of less than 35,000/uL
- Absolute Neutrophil Count (ANC) of less than 250/uL
- Serum Creatinine >2.0
- Serum total bilirubin >1.5 x upper limit of normal (ULN)
- Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of CMML within 28 days of the first day of study drug treatment
- Any serious medical condition or psychiatric illness that will prevent the subject from signing the informed consent form or will place the subject at unacceptable risk if he/she participates in the study
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- Concurrent use of Granulocyte/macrophage colony stimulating factor (GM-CSF). Granulocyte colony-stimulating factor (G-CSF) could be used for the short-term management of neutropenic infection. Stable doses of erythropoietin stimulating agents that were started >8 weeks from first ruxolitinib dose or corticosteroids that were being administered prior to screening are allowed.
- Uncontrolled current 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 because ruxolitinib has not been studied in pregnant subjects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with ruxolitinib, breastfeeding should be discontinued if the mother is treated with ruxolitinib.
- Patients who have participated in other interventional (treatment-related) clinical trials within 30 days of enrollment are excluded.
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
United States6 sites
Johns Hopkins Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, 21287
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Cleveland Clinic
Cleveland, Ohio, 44106
Weill Medical College of Cornell
New York, New York, 10021
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML) and Cataloging the Molecular Consequences of JAK2 Inhibition in Chronic Myelomonocytic Leukemia: A Correlative Study Identifying Targetable CMML Sub-Clones by Leveraging GM-CSF Dependent pSTAT Hypersensitivity
The purpose of this study is to find out if treating Chronic Myelomonocytic Leukemia (CMML) with a study drug [ruxolitinib] can improve outcomes of patients with CMML. The first step of the study is to learn the dose of ruxolitinib that is tolerable (bearable). It has already been studied in a number of patients with different bone marrow diseases and is approved for the treatment of a disease called Myelofibrosis; however, it is not approved for treatment of CMML. It is given orally (by mouth). Most people tolerate it well but the tolerability has not been determined in patients with CMML. We will be testing different doses to determine how much of the medication people can tolerate (bear) before they develop side effects.
Read the detailed description
This is a phase 1/2, two-stage, sequential cohort dose escalation study. If dose escalation is completed as planned, no more than 53 subjects are expected to enroll onto this study at a rate of approximately 3 subjects every month. For the Phase 2 study the Simon's optimal two-stage design will be employed to test the null hypothesis that response rate (RR) equals to 10% versus the alternative that RR equals to 30%.
Demographic and clinical variables for the study patients will be summarized using descriptive statistics (mean, standard deviation, median, inter-quartile range, range, and frequency counts and percentages). Safety and efficacy data will be analyzed overall as well as separately for each dose cohort when appropriate.
- Conditions
- Myelomonocytic Leukemia
- Being tested
- Ruxolitinib
- Keywords
- Chronic Myelomonocytic Leukemia, CMML, Leukemia
- Medical subject headings
- Leukemia, Myelomonocytic, Chronic, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Also called Jakafi®, INCB-018424, Kinase Inhibitor
In Phase I, participants will be allocated to twice a day (BID) doses of 10 mg/d up to 40mg/d. The starting dose will be 10 mg/d (5mg BID). Each cohort will include up to 6 subjects. Once MTD is reached, 10 additional participants will be treated during the first stage of Phase II (stage 1) at the MTD.
| Study group | Role | What they receive |
|---|---|---|
| I: Dose Escalation - Ruxolitinib | Experimental | Phase I: Dose Escalation. In Phase I, participants will be allocated to dose levels starting at 10 mg/d (twice a day [BID] dosing) according to the "rolling six" Phase I design. Receives: Drug: Ruxolitinib |
| II: Maximum Tolerated Dose - Ruxolitinib | Experimental | Phase II: Treatment at Maximum Tolerated Dose (MTD). Receives: Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Maximum Tolerated Dose (MTD) of Ruxolitinib for the Treatment of Myelomonocytic Leukemia (CMML)
Phase I - The MTD is defined as the highest dose where less than 33% of participants experience a drug related predefined dose limited toxicity (DLT). Dose-limiting toxicity (DLT) is defined as any grade 4 hematologic toxicity and any grade 3 or greater non-hematologic toxicity except nausea that is controlled by antiemetic therapy based on the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 3 metabolic/electrolyte abnormalities that are not clinically significant, and are adequately controlled within 72 hours are not to be considered a DLT.
Measured: 17 weeks
Occurrence of Clinical Response
Phase II - Proportion of participants achieving clinical benefit defined as hematologic improvement, complete remission (CR), partial remission (PR), marrow complete remission (Marrow CR) or stable disease (SD) by the International Working Group (IWG) 2006 criteria. Erythroid Response for pretreatment hemoglobin < 11 g/dl; Platelet response for subjects with a pre-treatment platelet count < 50 x 10^9/L; Neutrophil response with pretreatment absolute neutrophil count (ANC) < 1 x 10^9/L.
Measured: Up to 2 years
Secondary outcomes (3)
Percentage of Participants With Acute Myeloid Leukemia (AML) Transformation
Phase II - To determine the time to AML transformation of participants on Ruxolitinib. Acute myeloid leukemia (AML) transformation according to World Health Organization (WHO) criteria. CMML-1: peripheral blood <5% blasts, bone marrow <10% myeloblast. CMML-2: peripheral blood <19 percent blasts persistent monocytosis >1000/ul +/- cytopenias Leukocytosis frequent, bone marrow <19 percent blasts >10% dysplasia in affected lineage, Auer Rods.
Measured: Up to 2 years
Median Overall Survival (OS)
Phase II - To determine the median overall survival.
Measured: Up to 2 years
Duration of Response in Days
Phase II - To determine the duration of response achieved as in secondary endpoint one. The duration of response is measured from the time measurement criteria are met for major or complete platelet response (which ever is first recorded) until the first date that disease progression defined by the bone marrow response outlined above, progression/relapse following a CR, marrow CR or PR, or progressions/relapse following hematological improvement (HI) as outlined above.
Measured: 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2013 (estimated)
- Study start20 Feb 2013
- Primary completion28 Nov 2018
- Study completion10 May 2022
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.
- Other trials for Myelomonocytic LeukemiaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation
- Responsible party
- Sponsor
- Investigators
- Eric Padron, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01776723
- Sponsor's protocol ID
- MCC-17259
- Status last verified
- Sep 2022
- First submitted
- 24 Jan 2013
- Last updated
- 22 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Sequential Two-Stage Dose Escalation Study to Evaluate the Safety and Efficacy of Ruxolitinib for the Treatment of Chronic Myelomonocytic Leukemia (CMML) and Cataloging the Molecular Consequences of JAK2 Inhibition in Chronic Myelomonocytic Leukemia: A Correlative Study Identifying Targetable CMML Sub-Clones by Leveraging GM-CSF Dependent pSTAT Hypersensitivity
- ClinicalTrials.gov ID
- NCT01776723
- Acronym / sponsor ID
- MCC-17259
- Conditions
- Myelomonocytic Leukemia
- Keywords
- Chronic Myelomonocytic Leukemia, CMML, Leukemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Collaborators
- Incyte Corporation
- Study start
- 20 Feb 2013 (actual)
- Primary completion
- 28 Nov 2018 (actual)
- Study completion
- 10 May 2022 (actual)
- First posted
- 28 Jan 2013 (estimated)
- Results
- Posted 12 Mar 2020
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 find out if treating Chronic Myelomonocytic Leukemia (CMML) with a study drug [ruxolitinib] can improve outcomes of patients with CMML. The first step of the study is to learn the dose of ruxolitinib that is tolerable (bearable). It has already been studied in a number of patients with different bone marrow diseases and is approved for the treatment of a disease called Myelofibrosis; however, it is not approved for treatment of CMML. It is given orally (by mouth). Most people tolerate it well but the tolerability has not been determined in patients with CMML. We will be testing different doses to determine how much of the medication people can tolerate (bear) before they develop side effects.
Detailed description
This is a phase 1/2, two-stage, sequential cohort dose escalation study. If dose escalation is completed as planned, no more than 53 subjects are expected to enroll onto this study at a rate of approximately 3 subjects every month. For the Phase 2 study the Simon's optimal two-stage design will be employed to test the null hypothesis that response rate (RR) equals to 10% versus the alternative that RR equals to 30%.
Demographic and clinical variables for the study patients will be summarized using descriptive statistics (mean, standard deviation, median, inter-quartile range, range, and frequency counts and percentages). Safety and efficacy data will be analyzed overall as well as separately for each dose cohort when appropriate.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| I: Dose Escalation - Ruxolitinib | Experimental | Drug: RuxolitinibPhase I: Dose Escalation. In Phase I, participants will be allocated to dose levels starting at 10 mg/d (twice a day [BID] dosing) according to the "rolling six" Phase I design. |
| II: Maximum Tolerated Dose - Ruxolitinib | Experimental | Drug: RuxolitinibPhase II: Treatment at Maximum Tolerated Dose (MTD). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Confirmed diagnosis of CMML using the World Health Organization (WHO) classification
- Age >18 years at the time of obtaining informed consent
- Must be able to adhere to the study visit schedule and other protocol requirements
- Must be able to provide adequate bone marrow (BM) aspirate and biopsy specimens for histopathological analysis and standard cytogenetic analysis during the screening procedure
- An Eastern Cooperative Oncology Group (ECOG) performance status score of 0,1, or 2
Key exclusion criteria (10 listed)
- Platelet count of less than 35,000/uL
- Absolute Neutrophil Count (ANC) of less than 250/uL
- Serum Creatinine >2.0
- Serum total bilirubin >1.5 x upper limit of normal (ULN)
- Use of cytotoxic chemotherapeutic agents, or experimental agents (agents that are not commercially available) for the treatment of CMML within 28 days of the first day of study drug treatment
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 |
|---|---|---|
| RuxolitinibAlso: Jakafi®, INCB-018424, Kinase InhibitorIn Phase I, participants will be allocated to twice a day (BID) doses of 10 mg/d up to 40mg/d. The starting dose will be 10 mg/d (5mg BID). Each cohort will include up to 6 subjects. Once MTD is reached, 10 additional participants will be treated during the first stage of Phase II (stage 1) at the MTD. | Drug | I: Dose Escalation - Ruxolitinib, II: Maximum Tolerated Dose - Ruxolitinib |
Primary outcome
The Maximum Tolerated Dose (MTD) of Ruxolitinib for the Treatment of Myelomonocytic Leukemia (CMML)
Time frame: 17 weeks
Phase I - The MTD is defined as the highest dose where less than 33% of participants experience a drug related predefined dose limited toxicity (DLT). Dose-limiting toxicity (DLT) is defined as any grade 4 hematologic toxicity and any grade 3 or greater non-hematologic toxicity except nausea that is controlled by antiemetic therapy based on the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Grade 3 metabolic/electrolyte abnormalities that are not clinically significant, and are adequately controlled within 72 hours are not to be considered a DLT.
Occurrence of Clinical Response
Time frame: Up to 2 years
Phase II - Proportion of participants achieving clinical benefit defined as hematologic improvement, complete remission (CR), partial remission (PR), marrow complete remission (Marrow CR) or stable disease (SD) by the International Working Group (IWG) 2006 criteria. Erythroid Response for pretreatment hemoglobin < 11 g/dl; Platelet response for subjects with a pre-treatment platelet count < 50 x 10^9/L; Neutrophil response with pretreatment absolute neutrophil count (ANC) < 1 x 10^9/L.
3 secondary outcomes
Percentage of Participants With Acute Myeloid Leukemia (AML) Transformation
Time frame: Up to 2 years
Median Overall Survival (OS)
Time frame: Up to 2 years
Duration of Response in Days
Time frame: 3.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Eric Padron, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ruxolitinib in people with Myelomonocytic Leukemia, run by H. Lee Moffitt Cancer Center and Research Institute at 6 sites 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 8 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: finished, as of the sponsor's last update on 22 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites 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 combined 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.
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 12 Mar 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?
The Maximum Tolerated Dose (MTD) of Ruxolitinib for the Treatment of Myelomonocytic Leukemia (CMML) (time frame: 17 weeks). The study lists 2 primary outcomes in all. 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 22 Sep 2022; AzTrials last refreshed its copy on 31 Oct 2026.