Myeloproliferative NeoplasmPhase 1NCT05524857
Combination of Fedratinib and Decitabine for Myeloproliferative Neoplasms (MPN)- Accelerated Phase (AP)/Blast Phase (BP)
A Phase 1 study testing Fedratinib Oral Capsule 300 mg, Decitabine 20 mg/m2 and Fedratinib Oral Capsule 400 mg in people with Myeloproliferative Neoplasm, run by Joseph Jurcic at 1 site in United States.
Trial summary
The purpose of this research is to study the safety and tolerability and to establish the maximum tolerated dose (MTD) of the combination of two drugs, fedratinib and decitabine, for the treatment of advanced-phase MPNs. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myeloproliferative Neoplasm
- What is being tested?
- Fedratinib Oral Capsule 300 mg, Decitabine 20 mg/m2 and Fedratinib Oral Capsule 400 mg
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Jan 2022to 9 Apr 2024
- 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
- Subjects must have MPN-AP as defined by 10%-19% blasts in the peripheral blood or bone marrow and evidence of dysplastic marrow features with a concomitant diagnosis of essential thrombocythemia (ET), polycythemia vera (PV) or primary myelofibrosis (PMF) or a diagnosis of MPN-BP as defined by 20% blasts in the blood or bone marrow following a previous diagnosis of ET, PV or PMF.
- Subjects must have adequate organ function documented within 14 days of study entry as follows:
- Estimated creatinine clearance (by Cockcroft-Gault Equation) of ≥ 50 mL/min
- Serum total bilirubin ≤ 1.5 × ULN (unless attributable to Gilbert's disease or hemolysis, in which case the direct bilirubin level must be ≤ 1.5 × upper limit of normal (ULN)).
- Alkaline phosphatase, serum aspartate aminotransferase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN.
- ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2. Patients with ECOG performance status of 3 will be eligible if the lower performance status is deemed by the investigator to be due entirely to MPN-AP/BP and not due to another comorbidity.
Who cannot join
- Receipt of chemotherapy or investigational therapy, with the exception of hydroxyurea, within 4 weeks of study entry. Previous treatment at any time with decitabine, fedratinib or ruxolitinib as single agents will not exclude eligibility. Previous stem cell transplant will not exclude eligibility as long as other inclusion/exclusion criteria have been met and subjects do not have Grade ≥ II graft-versus-host disease (GVHD) requiring systemic immunosuppressive therapy.
- Subjects with an Human leukocyte antigen (HLA)-compatible donor or stem cell source who are immediate candidates for allogeneic hematopoietic cell transplantation (HCT).
- Subjects who are receiving any concurrent treatment for acute myeloid leukemia (AML), including other investigational agents.
- Diagnosis of acute myelofibrosis.
- Uncontrolled intercurrent illness including, but not limited to hepatitis, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class 3 or 4), unstable angina pectoris, ventricular arrhythmia, Child-Pugh Class C cirrhosis, or psychiatric illness/social situations that would limit compliance with study requirements.
- Subjects with a prior history of Wernicke's encephalopathy (WE) will be excluded. If a subject has signs or symptoms of encephalopathy, including Wernicke's encephalopathy (e.g. severe ataxia, ocular paralysis or cerebellar signs), thiamine deficiency must be excluded and a brain MRI should be obtained prior to study initiation to evaluate for WE.
- Other medications, severe acute/chronic medical or psychiatric conditions, or laboratory abnormalities that may increase the risk associated with study participation or study drug administration, or may interfere with the interpretation of study results, that in the judgment of the Investigator would make the subject inappropriate for entry into this study.
- Pregnant women are excluded because of the potential for teratogenic or abortifacient effects.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York Presbyterian Hospital/Columbia University Irving Medical Center
New York, New York, 10032
About this study
Official title: Phase I Trial of Fedratinib in Combination With Decitabine in Patients With Myeloproliferative Neoplasms in Accelerated and Blast Phase
The purpose of this research is to study the safety and tolerability and to establish the maximum tolerated dose (MTD) of the combination of two drugs, fedratinib and decitabine, for the treatment of advanced-phase MPNs.
Read the detailed description
This is a single center phase I dose-escalation trial of Fedratinib in Combination with Decitabine in Patients with Myeloproliferative Neoplasms. The primary objective is to determine the maximum tolerated dose of the combination therapy, using a 3+3 dose escalation algorithm. Fedratinib will be administered at 2 dose levels: 300 mg and 400 mg by mouth, once daily. Fedratinib will be administered concomitantly with decitabine 20 mg/m2 intravenously over 1 hour per day for 5 days in 28-day cycles.
- Conditions
- Myeloproliferative Neoplasm
- Being tested
- Fedratinib Oral Capsule 300 mg, Decitabine 20 mg/m2, Fedratinib Oral Capsule 400 mg
- Keywords
- Blast Phase, Fedratinib, Decitabine
- Medical subject headings
- Myeloproliferative Disorders, Blast Crisis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fedratinib Oral Capsule 300 mgDrug
Also called Inrebic
300 mg by mouth, once daily
Decitabine 20 mg/m2Drug
Also called Dacogen
20 mg/m2 for injection, for intravenous use
Fedratinib Oral Capsule 400 mgDrug
Also called Inrebic
400 mg by mouth, once daily
| Study group | Role | What they receive |
|---|---|---|
| Fedratinib 300 mg | Experimental | Cohort 1: 300 mg of Fedratinib by mouth, once daily during each 28-day cycle Receives: Drug: Fedratinib Oral Capsule 300 mg; Drug: Decitabine 20 mg/m2 |
| Fedratinib 400 mg | Experimental | Cohort 2: 400 mg of Fedratinib by mouth, once daily during each 28-day cycle Receives: Drug: Decitabine 20 mg/m2; Drug: Fedratinib Oral Capsule 400 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerated Dose (MTD) of Decitabine and Fedratinib
The MTD will be determined using a 3+3 algorithm. If < 33% of the subjects enrolled at a dose level experience a dose-limiting toxicity (DLT), escalation to the next designated dose cohort will continue. If ≥ 33% of the subjects enrolled at a dose level experience a DLT, the previous dosing cohort will be considered the MTD. DLT is defined as: (1) Grade 3, 4, or 5 non-hematologic toxicity considered at least possibly related to the study drug, except for infection, bleeding, fever, fatigue, dyspnea, and (2) Grade 3, 4, or 5 anemia, neutropenia or thrombocytopenia with a hypocellular bone marrow and < 5% marrow blasts lasting for 42 days or more.
Measured: Up to 8 weeks for each dosing cohort
Secondary outcomes (5)
Complete Remission (CR) Rate
Complete remission defined as participants that are free of all symptoms related to leukemia and have an absolute neutrophil count ≥ 1 x 10^9/L, no need for red blood cell transfusion, platelet count ≥ 100 x 10^9/L, and normal marrow differential (≤ 5 % blasts) in a normo- or hypercellular marrow.
Measured: Up to 3 years
Composite Complete Remission (CRc) Rate
CRc defined as (CR + Complete remission with incomplete count recovery (CRi)). CRi defined as CR but incomplete count recovery (absolute neutrophil count < 1000/microL or platelet count < 100,000/micro/L).
Measured: Up to 3 years
Partial Remission (PR) Rate
PR defined as CR with 6 - 25 % abnormal cells in the marrow or 50 % decrease in bone marrow blasts.
Measured: Up to 3 years
Progression Free Survival (PFS)
PFS is defined as the duration of time from entry on study to time of recurrence, flow cytometric relapse, cytogenetic relapse, molecular relapse, or death, whichever occurs first.
Measured: Up to 3 years
Overall Survival (OS)
OS is defined as the duration of time from entry on study to time of death from any cause.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Sep 2022
- Study start28 Jan 2022
- Primary completion9 Apr 2024
- Study completion9 Apr 2024
Why it stopped: Closed by Sponsor
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Joseph Jurcic
- Sponsor type
- University, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Responsible party
- Sponsor-investigator, Joseph Jurcic, Columbia University
- Investigators
- Joseph Jurcic, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05524857
- Sponsor's protocol ID
- AAAT9407
- Status last verified
- Apr 2024
- First submitted
- 30 Aug 2022
- Last updated
- 23 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Trial of Fedratinib in Combination With Decitabine in Patients With Myeloproliferative Neoplasms in Accelerated and Blast Phase
- ClinicalTrials.gov ID
- NCT05524857
- Acronym / sponsor ID
- AAAT9407
- Conditions
- Myeloproliferative Neoplasm
- Keywords
- Blast Phase, Fedratinib, Decitabine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Closed by Sponsor
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Joseph JurcicUniversity, hospital or other
- Collaborators
- Bristol-Myers Squibb
- Study start
- 28 Jan 2022 (actual)
- Primary completion
- 9 Apr 2024 (actual)
- Study completion
- 9 Apr 2024 (actual)
- First posted
- 1 Sep 2022 (actual)
- 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.
The purpose of this research is to study the safety and tolerability and to establish the maximum tolerated dose (MTD) of the combination of two drugs, fedratinib and decitabine, for the treatment of advanced-phase MPNs.
Detailed description
This is a single center phase I dose-escalation trial of Fedratinib in Combination with Decitabine in Patients with Myeloproliferative Neoplasms. The primary objective is to determine the maximum tolerated dose of the combination therapy, using a 3+3 dose escalation algorithm. Fedratinib will be administered at 2 dose levels: 300 mg and 400 mg by mouth, once daily. Fedratinib will be administered concomitantly with decitabine 20 mg/m2 intravenously over 1 hour per day for 5 days in 28-day cycles.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fedratinib 300 mg | Experimental | Drug: Fedratinib Oral Capsule 300 mg, Drug: Decitabine 20 mg/m2Cohort 1: 300 mg of Fedratinib by mouth, once daily during each 28-day cycle |
| Fedratinib 400 mg | Experimental | Drug: Decitabine 20 mg/m2, Drug: Fedratinib Oral Capsule 400 mgCohort 2: 400 mg of Fedratinib by mouth, once daily during each 28-day cycle |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Subjects must have MPN-AP as defined by 10%-19% blasts in the peripheral blood or bone marrow and evidence of dysplastic marrow features with a concomitant diagnosis of essential thrombocythemia (ET), polycythemia vera (PV) or primary myelofibrosis (PMF) or a diagnosis of MPN-BP as defined by 20% blasts in the blood or bone marrow following a previous diagnosis of ET, PV or PMF.
- Subjects must have adequate organ function documented within 14 days of study entry as follows:
- ≥ 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) Performance status of 0-2. Patients with ECOG performance status of 3 will be eligible if the lower performance status is deemed by the investigator to be due entirely to MPN-AP/BP and not due to another comorbidity.
Key exclusion criteria (8 listed)
- Receipt of chemotherapy or investigational therapy, with the exception of hydroxyurea, within 4 weeks of study entry. Previous treatment at any time with decitabine, fedratinib or ruxolitinib as single agents will not exclude eligibility. Previous stem cell transplant will not exclude eligibility as long as other inclusion/exclusion criteria have been met and subjects do not have Grade ≥ II graft-versus-host disease (GVHD) requiring systemic immunosuppressive therapy.
- Subjects with an Human leukocyte antigen (HLA)-compatible donor or stem cell source who are immediate candidates for allogeneic hematopoietic cell transplantation (HCT).
- Subjects who are receiving any concurrent treatment for acute myeloid leukemia (AML), including other investigational agents.
- Diagnosis of acute myelofibrosis.
- Uncontrolled intercurrent illness including, but not limited to hepatitis, human immunodeficiency virus (HIV)-positive subjects receiving combination antiretroviral therapy, ongoing or active infection, symptomatic congestive heart failure (New York Heart Association Class 3 or 4), unstable angina pectoris, ventricular arrhythmia, Child-Pugh Class C cirrhosis, 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 |
|---|---|---|
| Fedratinib Oral Capsule 300 mgAlso: Inrebic300 mg by mouth, once daily | Drug | Fedratinib 300 mg |
| Decitabine 20 mg/m2Also: Dacogen20 mg/m2 for injection, for intravenous use | Drug | Fedratinib 300 mg, Fedratinib 400 mg |
| Fedratinib Oral Capsule 400 mgAlso: Inrebic400 mg by mouth, once daily | Drug | Fedratinib 400 mg |
Primary outcome
Maximum Tolerated Dose (MTD) of Decitabine and Fedratinib
Time frame: Up to 8 weeks for each dosing cohort
The MTD will be determined using a 3+3 algorithm. If < 33% of the subjects enrolled at a dose level experience a dose-limiting toxicity (DLT), escalation to the next designated dose cohort will continue. If ≥ 33% of the subjects enrolled at a dose level experience a DLT, the previous dosing cohort will be considered the MTD. DLT is defined as: (1) Grade 3, 4, or 5 non-hematologic toxicity considered at least possibly related to the study drug, except for infection, bleeding, fever, fatigue, dyspnea, and (2) Grade 3, 4, or 5 anemia, neutropenia or thrombocytopenia with a hypocellular bone marrow and < 5% marrow blasts lasting for 42 days or more.
5 secondary outcomes
Complete Remission (CR) Rate
Time frame: Up to 3 years
Composite Complete Remission (CRc) Rate
Time frame: Up to 3 years
Partial Remission (PR) Rate
Time frame: Up to 3 years
Progression Free Survival (PFS)
Time frame: Up to 3 years
Overall Survival (OS)
Time frame: Up to 3 years
Results and safety
The study was stopped early (reason given: Closed by Sponsor). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2024.
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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.
Joseph Jurcic, MD principal investigator
Columbia University
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 Fedratinib Oral Capsule 300 mg, Decitabine 20 mg/m2 and Fedratinib Oral Capsule 400 mg in people with Myeloproliferative Neoplasm, run by Joseph Jurcic 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 7 inclusion and 8 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 23 Apr 2024. 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: Closed by Sponsor). 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?
Maximum Tolerated Dose (MTD) of Decitabine and Fedratinib (time frame: Up to 8 weeks for each dosing cohort). 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 23 Apr 2024.