Fedratinib in Combination With Nivolumab
A multicenter, open-label, single arm, phase II study investigating the clinical efficacy of Fedratinib and Nivolumab combination in patients with myelofibrosis and resistance or suboptimal response to JAK-inhibitor treatment
Accepts Healthy Volunteers
Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms
An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.
An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.
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|Eligible Ages||18 Years and Over|
Inclusion Criteria:1. Signed Informed Consent Form available and patient willing and able to adhere to the study visit schedule and other protocol requirements. 2. Patients* ≥18 years of age. 3. diagnosed with myelofibrosis (MF) according to the WHO 2008 or 2016 criteria, including primary (pre-fibrotic or overt) and secondary myelofibrosis. 4. Patients with an indication for therapy (either symptomatic patients with splenomegaly >11cm diameter and/or symptoms restricting their daily activity or patients with DIPSS int-2, or high risk or MIPSS70 int or high) 5. Patients with no response or suboptimal response to any JAK-inhibitor therapy (regarding persistence of symptoms, splenomegaly, cytopenia or hyperproliferation) defined either by.
- - Persisting Splenomegaly >11cm total diameter.
- - Persisting leukoerythroblastosis.
- - Anemia <6.2 mmol/l (<10g/dl) - Elevated WBC (>11 Gpt/l) - Persisting general or constitutional symptoms (persistence is defined as less than 50% reduction to baseline when using the MPN10 TSS Score) OR failure [secondary resistance] to JAK-inhibitor treatment as defined by IWG-MRT criteria.
Exclusion Criteria:1. Planned hematopoietic stem cell transplantation within 3 months and suitable donor available. 2. >10% blasts in bone marrow smear (cytology) or >2x in blood smear within the screening phase or >20% blasts at any time in bone marrow or peripheral blood smears. 3. Creatinine >2xULN and Creatinine-Clearance <45ml/min; ALAT, ASAT & bilirubin >3xULN (if MF impact on liver >5xULN) 4. Baseline platelets count below 50 x 10^9/L and ANC < 1.0 x 10^9/L. 5. Diagnosis of PV, ET (according to WHO 2016) or positive molecular test for BCR-ABL. 6. Patients on ongoing medication for myelofibrosis including systemic corticosteroids (detailed list of permitted medications is provided in paragraph 220.127.116.11 and Appendix V) 7. Uncontrolled infection. 8. Evidence of acute or chronic infection with hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or tuberculosis. 9. Current participation in any other interventional clinical study within 30 days before the first administration of the investigational product or at any time during the study, unless it is an observational (non-interventional) study, or during the follow-up period of an interventional study with last dose of investigational product ≥30 days prior first administration of investigational product within this study. 10. No consent for registration, storage and processing of the individual disease characteristics and course as well as information of the family physician about study participation. 11. No consent for biobanking of patient's biological specimens. 12. Prior therapy with checkpoint-inhibitors. 13. Vaccination within 4 weeks prior to treatment start. 14. Hypersensitivity to the IMPs or to any of the excipients. 15. History of or uncontrolled autoimmune disease such as autoimmune-hepatitis, -pneumonitis, -thyroiditis, chronic inflammatory bowel disease, multiple sclerosis, or rheumatologic diseases (including but not limited to systemic lupus and vasculitis) 16. History of malignancy except for i) adequately treated local basal cell or squamous cell carcinoma of the skin, ii) asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥ 1 year prior to randomization, or iii) any other cancer that has been in complete remission for ≥ 5 years. 17. Secondary malignancy that limits survival to less than 6 months. 18. Drug or alcohol abuse within the last 6 months. 19. Patients who cannot adhere to the Pregnancy Prevention Plan. 20. Pregnant or breast-feeding females. 21. Thiamine levels below normal limit despite supplementation. 22. Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [§ 40 Abs. 1 S. 3 Nr. 3a AMG]
This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.
Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.
Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.
Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.
Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.
The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.
|Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest|
The person who is responsible for the scientific and technical direction of the entire clinical study.
|Salah-Eddin Al-Batran, Prof. Dr.|
|Principal Investigator Affiliation||Institut für Klinische Krebsforschung IKF GmbH|
Category of organization(s) involved as sponsor (and collaborator) supporting the trial.
The disease, disorder, syndrome, illness, or injury that is being studied.
|Primary Myelofibrosis, Secondary Myelofibrosis|
The FRACTION trial will evaluate the clinical efficacy of Fedratinib and Nivolumab combination therapy in patients with primary and secondary myelofibrosis based on the consensus criteria of the International Working Group for Myelofibrosis Research and treatment (IWG-MRT), extended by the criterion RBC-transfusion independence (RBC-TI).
Fedratinib (Cycle 1: Run-in-Phase with 400 mg QD for 4 weeks, Cycle 2-12: 400 mg QD, Dose modifications will be allowed based on observed toxicity to a 300 mg or a 200 mg daily dose) + Nivolumab (Cycle 2-12: 240 mg, i.v., q2w) Patients will receive study treatment until loss of response, death or study discontinuation for other reasons.
Drug: - Fedratinib Oral Capsule [Inrebic]
400 mg once daily p.o. from cycle 1-n, dose adjustment will be made according to the protocol
Drug: - Nivolumab
240 mg every 2 weeks i.v. from cycle 2-n
Contact a Trial Team
If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.
University Medicine Greifswald
Florian Heidel, Prof. Dr.
Universitätsklinikum Halle (Saale)
Halle (Saale), ,
Haifa Kathrin Al-Ali, Dr.