Fedratinib in Combination With Nivolumab

NCT05393674 | Completed Phase 2 DMC

• 1 other identifier: FRACTION_2021
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 7

Brief Summary

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

Conditions

Primary Myelofibrosis; Secondary Myelofibrosis

Keywords

MF; Fedratinib; JAK-inhibitor; Nivolumab

Outcome Measures

Primary Outcomes (1)

• Best response rate within 12 treatment cycles

  Best response rate within 12 treatment cycles according to the IWG-MRT criteria (including complete remission, CR, partial remission, PR, clinical improvement, CI, stable disease, SD 1, and red cell transfusion (RCT) independency according to Gale et al.)

  12 months after therapy start.

Secondary Outcomes (9)

• Safety: Incidence and severity of adverse events according to CTC criteria

  From informed consent until 100 days after last study drug

• Safety: Timing of adverse events according to CTC criteria

  From informed consent until 100 days after last study drug

• Safety: Incidence of Laboratory abnormalities

  From informed consent until 100 days after last study drug

• Safety: leukemic transformation

  From informed consent until 100 days after last study drug

• Clinical benefit

  3.5 years

Study Arms (1)

Experimental

EXPERIMENTAL

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]; Drug: Nivolumab

Interventions

Nivolumab DRUG

240 mg every 2 weeks i.v. from cycle 2-n

Experimental

Fedratinib Oral Capsule [Inrebic] DRUG

400 mg once daily p.o. from cycle 1-n, dose adjustment will be made according to the protocol

Experimental

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed Informed Consent Form available and patient willing and able to adhere to the study visit schedule and other protocol requirements.
• Patients\* ≥18 years of age
• diagnosed with myelofibrosis (MF) according to the WHO 2008 or 2016 criteria, including primary (pre-fibrotic or overt) and secondary myelofibrosis.
• 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)
• 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
• OR Persisting leukoerythroblastosis
• OR Anemia \<6.2 mmol/l (\<10g/dl)
• OR Elevated WBC (\>11 Gpt/l)
• OR 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.
• ECOG performance status \<3 at screening and adequate organ function
• Reliable contraception should be maintained throughout the study and for 1 month after discontinuation of Fedratinib or 5 months after discontinuation of Nivolumab\*\*
• Subject must be willing to receive transfusion of blood products
• Thiamine levels not below lower limit of normal (prior substitution is possible)

You may not qualify if:

• Planned hematopoietic stem cell transplantation within 3 months and suitable donor available
• \>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
• Creatinine \>2xULN and Creatinine-Clearance \<45ml/min; ALAT, ASAT \& bilirubin \>3xULN (if MF impact on liver \>5xULN)
• Baseline platelets count below 50 x 10\^9/L and ANC \< 1.0 x 10\^9/L
• Diagnosis of PV, ET (according to WHO 2016) or positive molecular test for BCR-ABL
• Patients on ongoing medication for myelofibrosis including systemic corticosteroids (detailed list of permitted medications is provided in paragraph 9.1.10.4 and Appendix V). Use of steroids within 14 days prior to the first dose of study drug and until end of treatment is prohibited by patients.
• Uncontrolled infection
• Evidence of acute or chronic infection with hepatitis B, hepatitis C, human immunodeficiency virus (HIV) or tuberculosis
• 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.
• 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
• No consent for biobanking of patient's biological specimens
• Prior therapy with checkpoint-inhibitors
• Vaccination within 4 weeks prior to treatment start
• Hypersensitivity to the IMPs or to any of the excipients
• 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)

Sponsors & Collaborators

• Prof. F. Heidel, MH Hannover: collaborator
• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Celgene International II S.á.r.l.: collaborator

Study Sites (7)

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

University Medicine Greifswald

Greifswald, Germany

Location

Universitätsklinikum Halle (Saale)

Halle, Germany

Location

Medizinische Hochschule

Hanover, Germany

Location

Universitätsklinikum Schleswig-Holstein

Lübeck, Germany

Location

Johannes Wesling Klinikum

Minden, Germany

Location

Uniklinik Ulm

Ulm, Germany

Location

Related Publications (1)

• Isfort S, von Bubnoff N, Al-Ali HK, Becker H, Gotze T, le Coutre P, Griesshammer M, Moskwa C, Wohn L, Riedel J, Palandri F, Manz K, Hochhaus A, Dohner K, Heidel FH. FRACTION: protocol of a phase II study of Fedratinib and Nivolumab combination in patients with myelofibrosis and resistance or suboptimal response to JAK-inhibitor treatment of the German MPN study group (GSG-MPN). Ann Hematol. 2024 Aug;103(8):2775-2785. doi: 10.1007/s00277-024-05867-w. Epub 2024 Jul 5.

  PMID: 38967662 RESULT

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

fedratinib; Nivolumab

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 17, 2022
• First Posted: May 26, 2022
• Study Start: June 14, 2022
• Primary Completion: November 5, 2025
• Study Completion: January 15, 2026
• Last Updated: April 8, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

DE (7)