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Primary MyelofibrosisPhase 2NCT05393674

Fedratinib in Combination With Nivolumab

A Phase 2 study testing Fedratinib Oral Capsule [Inrebic] and Nivolumab in people with Primary Myelofibrosis and Secondary Myelofibrosis, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 7 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Fedratinib Oral Capsule [Inrebic] and Nivolumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
7 sitesGermany
Study dates
14 Jun 2022to 15 Jan 2026
Phase
Phase 2
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

  • 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
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  • 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)
  • Normal nutritional status, as judged by the physician
  • Females of childbearing potential (FCBP) must undergo repetitive pregnancy testing (serum or urine) and pregnancy results must be negative.
  • Unless practicing complete abstinence from heterosexual intercourse, sexually active FCBP must agree to use adequate contraceptive methods (i.e. failure rate of < 1% per year).
  • Males (including those who have had a vasectomy) must use barrier contraception (condoms) when engaging in sexual activity with FCBP. Males must agree not to donate semen or sperm.

Who cannot join

  • 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.
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  • 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)
  • 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
  • Secondary malignancy that limits survival to less than 6 months.
  • Drug or alcohol abuse within the last 6 months
  • Patients who cannot adhere to the Pregnancy Prevention Plan
  • Pregnant or breast-feeding females
  • Thiamine levels below normal limit despite supplementation
  • 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]

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Germany7 sites

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau

  • University Medicine Greifswald

    Greifswald

  • Universitätsklinikum Halle (Saale)

    Halle

  • Medizinische Hochschule

    Hanover

  • Universitätsklinikum Schleswig-Holstein

    Lübeck

  • Johannes Wesling Klinikum

    Minden

  • Uniklinik Ulm

    Ulm

Other trials in Germany

About this study

Official title: A Phase II Study of Fedratinib and Nivolumab Combination in Patients With Myelofibrosis and Resistance or Suboptimal Response to JAK-inhibitor Treatment

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

Read the detailed description

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).

Being tested
Fedratinib Oral Capsule [Inrebic], Nivolumab
Keywords
MF, Fedratinib, JAK-inhibitor, Nivolumab
Medical subject headings
Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Fedratinib Oral Capsule [Inrebic]Drug

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

  • NivolumabDrug

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

Study groups in NCT05393674
Study groupRoleWhat they receive
ExperimentalExperimentalFedratinib (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.
Receives: Drug: Fedratinib Oral Capsule [Inrebic]; Drug: Nivolumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.)

    Measured: 12 months after therapy start.

Secondary outcomes (9)

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

    Incidence and severity of adverse events according to CTC criteria

    Measured: From informed consent until 100 days after last study drug

  2. Safety: Timing of adverse events according to CTC criteria

    Timing of adverse events according to CTC criteria

    Measured: From informed consent until 100 days after last study drug

  3. Safety: Incidence of Laboratory abnormalities

    Incidence of laboratory abnormalities including timing and relatedness.

    Measured: From informed consent until 100 days after last study drug

  4. Safety: leukemic transformation

    Cumulative incidence of leukemic transformation

    Measured: From informed consent until 100 days after last study drug

  5. Clinical benefit

    Proportion of patients with clinical benefit defined as stable disease (SD) plus hematologic improvement or stable disease (SD) plus improvement of MF-associated symptoms

    Measured: 3.5 years

  6. Efficacy: PFS

    Progression-free survival

    Measured: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 42 months

  7. Efficacy: Duration of response

    Time from first response including RBC-TI, CI, PR and CR (Appendix III) to date of loss of response. Times of patients without loss of response are censored at last tumor assessment.

    Measured: 3.5 years

  8. Efficacy: Overall survival

    Time from study entry to the last date known to be alive or death. Survival times of patients alive at last follow-up are censored.

    Measured: 3.5 years

  9. Efficacy: Disease burden

    Change of disease burden assessed by allelic ratio of the respective driver mutation and of high-risk mutations by next-generation sequencing [NGS]

    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.

  1. First posted26 May 2022
  2. Study start14 Jun 2022
  3. Primary completion5 Nov 2025
  4. Study completion15 Jan 2026

Resources

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
Masking
None (open label)
Enrolment
30 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05393674
Sponsor's protocol ID
FRACTION_2021
Status last verified
Dec 2025
First submitted
17 May 2022
Last updated
8 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared

Publications

  • 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.

    PubMed 38967662

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Fedratinib Oral Capsule [Inrebic] and Nivolumab in people with Primary Myelofibrosis and Secondary Myelofibrosis, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 7 sites in Germany.

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 19 inclusion and 22 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 8 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Germany. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Best response rate within 12 treatment cycles (time frame: 12 months after therapy start.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05393674, which also lists 1 linked publication.

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 8 Apr 2026.

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