Accelerated/Blast-phase Myeloproliferative NeoplasmPhase 2NCT04281498
Combined Ruxolitinib and Enasidenib in Patients With Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis With an IDH2 Mutation
A Phase 2 study testing Ruxolitinib and Enasidenib in people with Accelerated/Blast-phase Myeloproliferative Neoplasm and Chronic-phase Myelofibrosis, run by John Mascarenhas at 11 sites in 2 countries.
Trial summary
The presence of IDH mutation is associated with worse survival in patients with myelofibrosis. Moreover IDH mutations are among the most frequently encountered events in MPNs that have progressed to acute myeloid leukemia. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Accelerated/Blast-phase Myeloproliferative Neoplasm, Chronic-phase Myelofibrosis, IDH2 Mutation
- What is being tested?
- Ruxolitinib and Enasidenib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 11 sitesin 2 countries
- Study dates
- 14 Jan 2021to 30 May 2023
- 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
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Subjects must be ≥ 18 years at the time of signing the Informed Consent Form (ICF).
- Understanding and voluntary signing an IRB-approved informed consent form.
- Diagnosis of:
- Accelerated-phase (≥ 10% blasts in PB or BM) or blast-phase (≥ 20% blasts in PB or BM) myeloproliferative neoplasm (with history of prior myelofibrosis, polycythemia vera, or essential thrombocythemia)
- Previously treated patients with myelofibrosis with persistent disease or progressive disease (persistent or progressive splenomegaly, leukocytosis, anemia, or thrombocytopenia) with intermediate-1 or greater risk disease according to 2013 International Working Group (IWG) criteria, and 4-9% circulating blasts.
- Demonstration of an IDH2 mutation.
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- Platelet count > 75,000 X 109/L for chronic phase myelofibrosis patients.
- Prior therapy with either ruxolitinib or enasidenib is permitted, but not a combination of ruxolitinib and enasidenib.
- Patients with chronic phase myelofibrosis on ruxolitinib must be on the drug for at least 3 months and on a stable dose for at least one month.
- Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. ECOG 3 status will be allowed if attributable to MPN.
- Patients must have adequate organ function as demonstrated by the following: a. Direct bilirubin < 2.0mg/dL, unless due to Gilbert's disease or current elevations in direct bilirubin associated with existing enasidenib use. b. Serum creatinine< 2.0 mg/dL. c. ALT and AST ≤ 3x upper limit of normal (unless transaminitis is considered to be related to MF).
- Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to starting enasidenib and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking enasidenib. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a condom during sexual contact with a female of child bearing potential even if they have had a successful vasectomy. All patients must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.
- All study participants must be able to swallow oral medication.
- Ability to adhere to the study visit schedule and all protocol requirements.
Who cannot join
- Use of any other standard anti-neoplastic drug or growth factor (e.g., anagrelide, G-CSF, lenalidomide, thalidomide clofarabine) except hydroxyurea or experimental drugs, with the exception of ruxolitinib or enasidenib, less than 14 days or 5-half-lives, whichever is longer, prior to starting study therapy and/or lack of recovery from all toxicity (except for alopecia) from previous therapy to Grade 1 or better.
- Patients will be permitted to receive hydroxyurea while on study for up to a total of 3 cycles of combined therapy.
- Known prior clinically relevant hypersensitivity reaction to ruxolitinib or enasidenib.
- Prior therapy with enasidenib in combination with ruxolitinib.
- Concurrent use of strong inducers of CYP3A4 (Rifampin, St. John's Wort, Carbamazepine, Phenytoin) and/or the following strong inhibitors of CYP3A4 (protease inhibitor containing HIV anti-retrovirals, cobicistat, clarithromycin, itraconazole, ketoconazole, nefazodone, and telithromycin) are prohibited. Also prohibited are CYP2C9 substrate medications that have a narrow therapeutic range: phenytoin and warfarin.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form, which places the subject at unacceptable risk if he/she were to participate in the study or which confounds the ability to interpret data from the study.
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- Lactating females.
- Active uncontrolled infections.
- Patients with active malignancy of other type than required for this study are not eligible with the exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast. Patients with malignancies with indolent behavior such as prostate cancer treated with radiation or surgery can be enrolled in the study as long as they have a reasonable expectation to have been cured with the treatment modality received.
- Subject has significant active cardiac disease within 6 months prior to the start of study treatment, including New York Heart Association (NYHA) Class III or IV congestive heart failure; acute coronary syndrome (ACS); and/or stroke; or left ventricular ejection fraction (LVEF) < 40% by echocardiogram (ECHO) or multi-gated acquisition (MUGA) scan obtained within 28 days prior to the start of study treatment.
- QTc interval (Fridericia's correction [QTcF]) > 450 ms
- All inclusion and exclusion criteria will be reviewed by the Investigator or qualified designee to ensure that the patient qualifies for the trial.
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States10 sites
University of Michigan Rogel Cancer Center
Ann Arbor, Michigan, 48109-5936
Taussig Cancer Center Institute
Cleveland, Ohio, 44195
Cedars-Sinai Medical Center
Los Angeles, California, 90048
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Mays Cancer Center at UT Health San Antonio
San Antonio, Texas, 78229
Mayo Clinic - Arizona
Scottsdale, Arizona, 85259
Moffitt Cancer Center
Tampa, Florida, 33612
University of Kansas Cancer Center
Westwood, Kansas, 66205
Wake Forest Baptist Health
Winston-Salem, North Carolina, 27157
About this study
Official title: A Phase II Open-label Study of Combined Ruxolitinib and Enasidenib in Patients With Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis With an IDH2 Mutation
The presence of IDH mutation is associated with worse survival in patients with myelofibrosis. Moreover IDH mutations are among the most frequently encountered events in MPNs that have progressed to acute myeloid leukemia. Ruxolitinib, a JAK1/2 inhibitor, and enasidenib an IDH2 inhibitor are effective and tolerable treatments for patients with myelofibrosis (MF) and acute myeloid leukemia (AML), respectively. The study team hypothesize that the combination of these agents in patients with MPN with an IDH2 mutation will improve the overall clinical response to therapy.
Read the detailed description
At this time, there is no standard medical treatment for MPN-AP/BP and most patients with accelerated and blast phase MPN do not respond well to treatment This is a phase II open-label study to evaluate the safety and efficacy of combined ruxolitinib and enasidenib in patients with accelerated/blast-phase myeloproliferative neoplasm or chronic phase myelofibrosis with high risk features and IDH2 mutation.
Ruxolitinib (Jakafi/Jakavi) is FDA approved for myelofibrosis and was shown to reduce splenomegaly and improve symptoms. Enasidenib is a potent inhibitor of the IDH2 mutant enzyme and is FDA approved for relapsed refractory AML where it showed effectivity.
Pre-clinical studies indicate increased disease mitigating effects with the combination of enasidenib and ruxolitinib.
This study will enroll up to 32 patients. Ruxolitinib and enasidenib will be given orally in 28-day cycles.
- Conditions
- Accelerated/Blast-phase Myeloproliferative Neoplasm, Chronic-phase Myelofibrosis, IDH2 Mutation
- Being tested
- Ruxolitinib, Enasidenib
- Keywords
- Phase II, Myelofibrosis, Therapeutic, Ruxolitinib, Enasidenib, IDH2
- Medical subject headings
- Primary Myelofibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Patients who are on ruxolitinib will continue their current dose. Patients who are not on ruxolitinib will receive ruxolitinib dosing based on platelet count
EnasidenibDrug
50mg -100mg daily
| Study group | Role | What they receive |
|---|---|---|
| Patients with MPN | Experimental | Ruxolitinib and Enasidenib combination therapy Receives: Drug: Ruxolitinib; Drug: Enasidenib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of MPN Participants With Response
The number of treated accelerated-phase and blast-phase MPN patients (primary cohort) that achieve a best response per 2013 International Working Group (IWG) criteria of either complete response (CR), Partial Response (PR), or complete response with incomplete recovery of counts (CRi), when treated with the combination of ruxolitinib with enasidenib within 6 cycles of combined therapy.
Complete Response with incomplete recovery of counts (CRi) - complete remission (<5% marrow blasts by morphology) with incomplete count recovery (platelet count <100 x 10^9^/L and/or absolute neutrophil count < 1 x 10^9^/L)
Complete Response (CR) - full marrow recovery; full count recovery; resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH
Partial Response (PR) - morphologic remission in the peripheral blood but not necessarily in the bone marrow; resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH
Measured: 6 Months
Secondary outcomes (2)
Number of MPN Participants With Blast Response
The number of treated accelerated-phase and blast-phase MPN patients that achieve complete (CBR) and partial blast response (PBR).
Measured: 6 Months
Number of MF-CP Participants With Any Response
The number of treated patients with MF-CP and 4%-9% circulating blasts that achieve complete response (CR) Partial Response (PR), clinical improvement (CI) with the combination of ruxolitinib and enasidenib within 6 cycles of combined therapy.
Measured: 6 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Feb 2020
- Study start14 Jan 2021
- Primary completion30 May 2023
- Study completion30 May 2023
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 Accelerated/Blast-phase Myeloproliferative NeoplasmStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single Arm open-label Study of Combined Ruxolitinib and Enasidenib in Patients with Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis with an IDH2 Mutation, Simons minimax design.
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- John Mascarenhas
- Sponsor type
- University, hospital or other
- Collaborators
- Celgene Corporation, Incyte Corporation, Myeloproliferative Neoplasms Research Consortium, National Institutes of Health (NIH), National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, John Mascarenhas, Icahn School of Medicine at Mount Sinai
- Investigators
- John Mascarenhas, MD, Study chair, Icahn School of Medicine at Mount SinaiRuben Mesa, MD, Study chair, Mays Cancer Center at UT HealthRonald Hoffman, MD, Study chair, Icahn School of Medicine at Mount SinaiMichal Bar-Natan, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04281498
- Sponsor's protocol ID
- GCO 07-0548-0008
- Other IDs
- P01CA108671, MPN-RC 119
- Status last verified
- Jan 2025
- First submitted
- 20 Feb 2020
- Last updated
- 4 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Open-label Study of Combined Ruxolitinib and Enasidenib in Patients With Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis With an IDH2 Mutation
- ClinicalTrials.gov ID
- NCT04281498
- Acronym / sponsor ID
- GCO 07-0548-0008
- Conditions
- Accelerated/Blast-phase Myeloproliferative Neoplasm, Chronic-phase Myelofibrosis, IDH2 Mutation
- Keywords
- Phase II, Myelofibrosis, Therapeutic, Ruxolitinib, Enasidenib, IDH2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- John MascarenhasUniversity, hospital or other
- Collaborators
- Celgene Corporation, Incyte Corporation, Myeloproliferative Neoplasms Research Consortium, National Institutes of Health (NIH), National Cancer Institute (NCI)
- Study start
- 14 Jan 2021 (actual)
- Primary completion
- 30 May 2023 (actual)
- Study completion
- 30 May 2023 (actual)
- First posted
- 24 Feb 2020 (actual)
- Results
- Posted 18 Dec 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The presence of IDH mutation is associated with worse survival in patients with myelofibrosis. Moreover IDH mutations are among the most frequently encountered events in MPNs that have progressed to acute myeloid leukemia. Ruxolitinib, a JAK1/2 inhibitor, and enasidenib an IDH2 inhibitor are effective and tolerable treatments for patients with myelofibrosis (MF) and acute myeloid leukemia (AML), respectively. The study team hypothesize that the combination of these agents in patients with MPN with an IDH2 mutation will improve the overall clinical response to therapy.
Detailed description
At this time, there is no standard medical treatment for MPN-AP/BP and most patients with accelerated and blast phase MPN do not respond well to treatment This is a phase II open-label study to evaluate the safety and efficacy of combined ruxolitinib and enasidenib in patients with accelerated/blast-phase myeloproliferative neoplasm or chronic phase myelofibrosis with high risk features and IDH2 mutation.
Ruxolitinib (Jakafi/Jakavi) is FDA approved for myelofibrosis and was shown to reduce splenomegaly and improve symptoms. Enasidenib is a potent inhibitor of the IDH2 mutant enzyme and is FDA approved for relapsed refractory AML where it showed effectivity.
Pre-clinical studies indicate increased disease mitigating effects with the combination of enasidenib and ruxolitinib.
This study will enroll up to 32 patients. Ruxolitinib and enasidenib will be given orally in 28-day cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single Arm open-label Study of Combined Ruxolitinib and Enasidenib in Patients with Accelerated/Blast-phase Myeloproliferative Neoplasm or Chronic-phase Myelofibrosis with an IDH2 Mutation, Simons minimax design.
| Arm | Type | Receives |
|---|---|---|
| Patients with MPN | Experimental | Drug: Ruxolitinib, Drug: EnasidenibRuxolitinib and Enasidenib combination therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Subjects must be ≥ 18 years at the time of signing the Informed Consent Form (ICF).
- Understanding and voluntary signing an IRB-approved informed consent form.
- Diagnosis of:
- Demonstration of an IDH2 mutation.
- Platelet count > 75,000 X 109/L for chronic phase myelofibrosis patients.
Key exclusion criteria (12 listed)
- Use of any other standard anti-neoplastic drug or growth factor (e.g., anagrelide, G-CSF, lenalidomide, thalidomide clofarabine) except hydroxyurea or experimental drugs, with the exception of ruxolitinib or enasidenib, less than 14 days or 5-half-lives, whichever is longer, prior to starting study therapy and/or lack of recovery from all toxicity (except for alopecia) from previous therapy to Grade 1 or better.
- Known prior clinically relevant hypersensitivity reaction to ruxolitinib or enasidenib.
- Prior therapy with enasidenib in combination with ruxolitinib.
- Concurrent use of strong inducers of CYP3A4 (Rifampin, St. John's Wort, Carbamazepine, Phenytoin) and/or the following strong inhibitors of CYP3A4 (protease inhibitor containing HIV anti-retrovirals, cobicistat, clarithromycin, itraconazole, ketoconazole, nefazodone, and telithromycin) are prohibited. Also prohibited are CYP2C9 substrate medications that have a narrow therapeutic range: phenytoin and warfarin.
- Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form, which places the subject at unacceptable risk if he/she were to participate in the study or which confounds the ability to interpret data from the study.
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 |
|---|---|---|
| RuxolitinibPatients who are on ruxolitinib will continue their current dose. Patients who are not on ruxolitinib will receive ruxolitinib dosing based on platelet count | Drug | Patients with MPN |
| Enasidenib50mg -100mg daily | Drug | Patients with MPN |
Primary outcome
Number of MPN Participants With Response
Time frame: 6 Months
The number of treated accelerated-phase and blast-phase MPN patients (primary cohort) that achieve a best response per 2013 International Working Group (IWG) criteria of either complete response (CR), Partial Response (PR), or complete response with incomplete recovery of counts (CRi), when treated with the combination of ruxolitinib with enasidenib within 6 cycles of combined therapy. Complete Response with incomplete recovery of counts (CRi) - complete remission (<5% marrow blasts by morphology) with incomplete count recovery (platelet count <100 x 10^9^/L and/or absolute neutrophil count < 1 x 10^9^/L) Complete Response (CR) - full marrow recovery; full count recovery; resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH Partial Response (PR) - morphologic remission in the peripheral blood but not necessarily in the bone marrow; resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH
2 secondary outcomes
Number of MPN Participants With Blast Response
Time frame: 6 Months
Number of MF-CP Participants With Any Response
Time frame: 6 Months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- 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.
John Mascarenhas, MD study chair
Icahn School of Medicine at Mount Sinai
Ruben Mesa, MD study chair
Mays Cancer Center at UT Health
Ronald Hoffman, MD study chair
Icahn School of Medicine at Mount Sinai
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ruxolitinib and Enasidenib in people with Accelerated/Blast-phase Myeloproliferative Neoplasm and Chronic-phase Myelofibrosis, run by John Mascarenhas at 11 sites in 2 countries.
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 12 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 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Canada. 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 18 Dec 2024). 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?
Number of MPN Participants With Response (time frame: 6 Months). 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 4 Feb 2025.