MyelofibrosisPhase 1/2ADORENCT04097821
Platform Study of Novel Ruxolitinib Combinations in Myelofibrosis Patients
A Phase 1/2 study testing Ruxolitinib, Siremadlin and Crizanlizumab in people with Myelofibrosis, run by Novartis Pharmaceuticals at 22 sites in 13 countries.
Trial summary
The purpose of this study was to investigate the safety, pharmacokinetics and preliminary efficacy of combination treatment of ruxolitinib with 5 novel compounds: siremadlin, crizanlizumab, sabatolimab, rineterkib and NIS793 in myelofibrosis (MF) subjects. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Myelofibrosis
- What is being tested?
- Ruxolitinib, Siremadlin and Crizanlizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 22 sitesin 13 countries
- Study dates
- 26 Sep 2019to 28 Aug 2024
- Phase
- Phase 1/2
- 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 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Core treatment phase Inclusion Criteria:
- Subjects have diagnosis of primary myelofibrosis (PMF) according to the 2016 World Health Organization (WHO) criteria, or diagnosis of post-essential thrombocythemia (ET) (PET-MF) or post-polycythemia vera (PV) myelofibrosis (PPV-MF) according to the International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) 2007 criteria
- Palpable spleen of at least 5 cm from the left costal margin (LCM) to the point of greatest splenic protrusion or enlarged spleen volume of at least 450 cm3 per MRI or CT scan at baseline (a MRI/CT scan up to 8 weeks prior to first dose of study treatment can be accepted).
- Have been treated with ruxolitinib for at least 12 weeks prior to first dose of study treatment
- Are stable (no dose adjustments) on the prescribed ruxolitinib dose (between 5 and 25 mg twice a day (BID)) for ≥ 4 weeks prior to first dose of study treatment
Extension treatment phase inclusion criteria:
- Signed consent for the extension treatment phase
- ongoing in the core treatment phase
- demonstrates clinical benefit of treatment in core treatment phase per investigator's assessment.
Core treatment phase Exclusion Criteria:
- Not able to understand and to comply with study instructions and requirements.
- Received any investigational agent for the treatment of MF (except ruxolitinib) within 30 days of first dose of study treatment or within 5 half-lives of the study treatment, whichever is greater
- Peripheral blood blasts count of > 10%.
- has documented severe hypersensitivity reactions/immunogenicity (IG) to a prior biologic product or Received a monoclonal antibody (Ab) or immunoglobulin-based agent within 1 year of screening in NIS793, crizanlizumab or sabatolimab arms, or in rineterkib or siremadlin arms within <=4 weeks of screening or <=5 half-lives whichever is shorter
- Splenic irradiation within 6 months prior to the first dose of study drug
- Received blood platelet transfusion within 28 days prior to first dose of study treatment.
Extension treatment phase Exclusion Criteria:
- meets any of study treatment discontinuation criteria
- current evidence of treatment failure per investigator, following treatment in core treatment phase
- enrolled in another interventional study
- evidence of non-compliance to study procedures or withdrew consent in core treatment phase
- currently has unresolved toxicities for which study treatment has been interrupted in the core treatment phase
- local access to alternative myelofibrosis treatment including those currently under investigation in clinical trials as assessed suitable in the opinion of the investigator.
Trial locations and contacts
22 sites in 13 countries.
22 sites in 13 countries
Germany4 sites
Novartis Investigative Site
Freiburg im Breisgau, 79106
Novartis Investigative Site
Greifswald, 17475
Novartis Investigative Site
Jena, 07740
Novartis Investigative Site
Mannheim, Baden-Wurttemberg, 68305
Spain4 sites
Novartis Investigative Site
Alicante, 03010
Novartis Investigative Site
Las Palmas de Gran Canaria, 35010
Novartis Investigative Site
Madrid, 28034
Novartis Investigative Site
Salamanca, Castille and León, 37007
Australia3 sites
Novartis Investigative Site
Adelaide, South Australia, 5000
Novartis Investigative Site
Melbourne, Victoria, 3000
Novartis Investigative Site
Melbourne, Victoria, 3004
Switzerland2 sites
Novartis Investigative Site
Sankt Gallen, 9007
Novartis Investigative Site
Zurich, 8091
About this study
Official title: A Randomized, Open-label, Phase I/II Open Platform Study Evaluating Safety and Efficacy of Novel Ruxolitinib Combinations in Myelofibrosis Patients
The purpose of this study was to investigate the safety, pharmacokinetics and preliminary efficacy of combination treatment of ruxolitinib with 5 novel compounds: siremadlin, crizanlizumab, sabatolimab, rineterkib and NIS793 in myelofibrosis (MF) subjects.
Read the detailed description
This open-label, multi-center, Phase Ib/II platform study design consisted of 3 parts. Part 1 was a Phase Ib dose escalation and safety run-in for the 5 novel agents in combination with ruxolitinib to assess safety, tolerability and to confirm a recommended Phase II dose. Dose escalation cohorts were treated with ruxoltinib + siremadlin or ruxolitinib + rineterkib. Safety run-in cohorts were treated with either ruxolitinb + sabatolimab, ruxolitinb + crizanlizumab or ruxolitinib + NIS7913.
Parts 2 and 3 were Phase II selection and expansion, respectively, to assess preliminary efficacy of the combination treatments from Part 1 that were evaluated as safe and tolerable. The number of combination treatment arms opening in Part 2 depended on the results of Part 1. In Part 2, an interim analysis was planned to determine if combination treatment(s) could be expanded in Part 3.
In June 2022, Novartis decided to permanently halt the study enrollment in all ongoing parts (Part 1 and Part 2), and Part 3 (expansion) was not initiated. With Protocol Amendment 8, an extension treatment phase of 12 cycles was added in Part 1 to allow access to the combination treatment for ongoing subjects deriving clinical benefit. In consideration of the enrollment halt, Parts 2 and 3 objectives were not pursued, and Part 1 objectives were updated accordingly.
- Conditions
- Myelofibrosis
- Being tested
- Ruxolitinib, Siremadlin, Crizanlizumab, Sabatolimab, Rineterkib
- Keywords
- myelofibrosis, ruxolitinib, INC424, siremadlin, HDM201, crizanlizumab, SEG101, sabatolimab, MBG453, rineterkib, LTT462, NIS793, platform study
- 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
Also called INC424, Jakavi
5 mg tablets for oral use
SiremadlinDrug
Also called HDM201
10 mg, 20 mg, or 40 mg capsules for oral use
CrizanlizumabDrug
Also called SEG101
100 mg/10 mL concentrate for infusion for intravenous use
SabatolimabDrug
Also called MBG453
100 mg/mL or 400 mg/4 mL concentrate for infusion for intravenous use
RineterkibDrug
Also called LTT462
100 mg capsule for oral use
NIS793Drug
700 mg/7 mL concentrate for infusion for intravenous use
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Ruxolitinib + Siremadlin 20 mg | Experimental | Dose escalation of siremadlin added to existing stable dose of ruxolitinib Receives: Drug: Ruxolitinib; Drug: Siremadlin |
| Part 1: Ruxolitinib + Siremadlin 30 mg | Experimental | Dose escalation of siremadlin added to existing stable dose of ruxolitinib Receives: Drug: Ruxolitinib; Drug: Siremadlin |
| Part 1: Ruxolitinib + Siremadlin 40 mg | Experimental | Dose escalation of siremadlin added to existing stable dose of ruxolitinib Receives: Drug: Ruxolitinib; Drug: Siremadlin |
| Part 1: Ruxolitinib + Rineterkib 200 mg | Experimental | Dose escalation of rineterkib added to existing stable dose of ruxolitinib Receives: Drug: Ruxolitinib; Drug: Rineterkib |
| Part 1: Ruxolitinib + Crizanlizumab | Experimental | Safety run-in of crizanlizumab added to existing stable dose of ruxolitinib Receives: Drug: Ruxolitinib; Drug: Crizanlizumab |
| Part 1: Ruxolitinib + Sabatolimab | Experimental | Safety run-in of sabatolimab added to existing stable dose of ruxolitinib Receives: Drug: Ruxolitinib; Drug: Sabatolimab |
| Part 1: Ruxolitinib + NIS793 | Experimental | Safety run-in of NIS793 added to existing stable dose of ruxolitinib Receives: Drug: Ruxolitinib; Drug: NIS793 |
| Part 2: Ruxolitinib | Active comparator | Existing stable dose of ruxolitinib as control for Part 2 Receives: Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1
Incidence and severity of dose limiting toxicities within the first 2 cycles (6 or 8 weeks) in Part 1 of the study. DLTs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria Version 5.0. Grade 0 was assigned for all non-missing values not graded as 1 or higher. Higher grade indicated more severity. Grade 5 was not used.
Measured: Baseline to the end of Cycle 2 (6 or 8 weeks)
Response Rate at the End of Cycle 6 or Cycle 8 in Part 1
Composite of anemia improvement (hemoglobin level) and no spleen volume progression and no symptom worsening in Part 2 and Part 3 of the study. For a subject to be considered a responder, all three components of the composite had to be fulfilled.
Measured: Baseline to the end of Cycle 6 or 8 (24 weeks)
Secondary outcomes (18)
Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1
Measured: Week 24, Week 48
Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1
Measured: Week 24, Week 48
Change in Spleen Length From Baseline in Part 1
Change in spleen length measured in centimeters by manual palpation.
Measured: Baseline, Week 24, Week 48
Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1
Change in spleen volume measured by magnetic resonance imaging (MRI) or computed tomography (CT) from baseline.
Measured: Week 24, Week 48
Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1
Change in spleen volume measured by magnetic resonance imaging (MRI) or computed tomography (CT) from baseline.
Measured: Week 24, Week 48
Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)
The MFSAF v4.0 questionnaire focuses on the 7 core symptoms of MF: fatigue, night sweats, pruritus, abdominal discomfort, pain under the ribs on the left side, early satiety and bone pain. Subjects record symptom severity at it worst for each of the 7 symptoms on an 11-point numeric rating scale, from 0 (absent) to 10 (worst imaginable). The Total Symptom Score (TSS) is the sum of all the scores for all 7 symptoms.
Measured: Week 12, Week 24, Week 48
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1
Measured: Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1
Measured: Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1
Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1
Measured: Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib
Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1
Measured: Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1
Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1
Measured: Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib
Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1
Measured: Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1
Concentration Versus Time Profile for Siremadlin in Part 1
Measured: Day 1 of Cycles 1 and 2; Day 6 of Cycle 1; Days 2 and 5 of Cycles 1, 2, 3, 4, 5, and 6. Each cycle was 28 days.
Concentration Versus Time Profile for Rineterkib in Part 1
Measured: Days 1, 2, 15, and 16 of Cycle 1; Day 1 of Cycles 2, 3, 4, 5, and 6. Each cycle was 28 days.
Concentration Versus Time Profile for Crizanlizumab in Part 1
EOI = end of infusion
Measured: Days 1, 2, 8, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4, 5, 6, and 9. Each cycle was 28 days.
Concentration Versus Time Profile for Sabatolimab in Part 1
EOI = end of infusion
Measured: Days 1, 2, 8, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4 and 5. Each cycle was 28 days.
Concentration Versus Time Profile for NIS793 in Part 1
EOI = end of infusion
Measured: Days 1, 2, 4, 8, 11, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4 and 5. Each cycle was 28 days.
Concentration Versus Time Profile for Ruxolitinib in Part 1
Measured: Days 1, 2, 5, 6, and 15 of Cycles 1 and 2; Day 16 of Cycle 1; Days 1, 2, and 15 of Cycle 3; Days 1 and 5 of Cycles 4, 5, and 6. Each cycle was 28 days.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2019
- Study start26 Sep 2019
- Primary completion3 May 2023
- Study completion28 Aug 2024
Why it stopped: Sponsor Decision
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for MyelofibrosisStudies of the same condition, open and under way.
- More trials run by Novartis PharmaceuticalsThe sponsor's other registered studies.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This open-label, multi-center, phase Ib/II platform study design consisted of 3 parts. Part 1 was a phase Ib dose escalation and safety run-in for the 5 novel agents in combination with ruxolitinib to assess safety, tolerability and to confirm recommended Phase II dose. Parts 2 and 3 were phase II selection and expansion respectively, to assess preliminary efficacy of the combination treatments from Part 1 that were evaluated as safe and tolerable. The number of combination treatment arms opening in Part 2 depended on the results of Part 1. In Part 2, interim analysis was planned to determine if combination treatment(s) could be expanded in Part 3.
- Masking
- None (open label)
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novartis Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Novartis Pharmaceuticals, Study director, Novartis Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04097821
- Sponsor's protocol ID
- CINC424H12201
- Other IDs
- 2019-000373-23, 2019
- Acronym
- ADORE
- Status last verified
- Jul 2025
- First submitted
- 17 Sep 2019
- Last updated
- 7 Aug 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
Publications
Ross DM, Heidel FH, Perkins AC, Reiter A, Crodel C, Riley C, Gomez-Casares MT, Takacs I, Becker H, Lehmann T, Vinogradova O, Burbury K, Vannucchi AM, Gupta V, Wondergem M, Kiladjian JJ, Cleary G, Zhang A, Kota J, Prahallad A, Wroclawska M, Lu M, Harrison CN. ADORE: an open platform study of ruxolitinib in combination with other novel therapies in patients with myelofibrosis. Blood Adv. 2025 Aug 26;9(16):4195-4205. doi: 10.1182/bloodadvances.2025015860.
PubMed 40334082
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label, Phase I/II Open Platform Study Evaluating Safety and Efficacy of Novel Ruxolitinib Combinations in Myelofibrosis Patients
- ClinicalTrials.gov ID
- NCT04097821
- Acronym / sponsor ID
- ADORE / CINC424H12201
- Conditions
- Myelofibrosis
- Keywords
- myelofibrosis, ruxolitinib, INC424, siremadlin, HDM201, crizanlizumab, SEG101, sabatolimab
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor Decision
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Novartis PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 26 Sep 2019 (actual)
- Primary completion
- 3 May 2023 (actual)
- Study completion
- 28 Aug 2024 (actual)
- First posted
- 20 Sep 2019 (actual)
- Results
- Posted 7 Aug 2025
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 study was to investigate the safety, pharmacokinetics and preliminary efficacy of combination treatment of ruxolitinib with 5 novel compounds: siremadlin, crizanlizumab, sabatolimab, rineterkib and NIS793 in myelofibrosis (MF) subjects.
Detailed description
This open-label, multi-center, Phase Ib/II platform study design consisted of 3 parts. Part 1 was a Phase Ib dose escalation and safety run-in for the 5 novel agents in combination with ruxolitinib to assess safety, tolerability and to confirm a recommended Phase II dose. Dose escalation cohorts were treated with ruxoltinib + siremadlin or ruxolitinib + rineterkib. Safety run-in cohorts were treated with either ruxolitinb + sabatolimab, ruxolitinb + crizanlizumab or ruxolitinib + NIS7913.
Parts 2 and 3 were Phase II selection and expansion, respectively, to assess preliminary efficacy of the combination treatments from Part 1 that were evaluated as safe and tolerable. The number of combination treatment arms opening in Part 2 depended on the results of Part 1. In Part 2, an interim analysis was planned to determine if combination treatment(s) could be expanded in Part 3.
In June 2022, Novartis decided to permanently halt the study enrollment in all ongoing parts (Part 1 and Part 2), and Part 3 (expansion) was not initiated. With Protocol Amendment 8, an extension treatment phase of 12 cycles was added in Part 1 to allow access to the combination treatment for ongoing subjects deriving clinical benefit. In consideration of the enrollment halt, Parts 2 and 3 objectives were not pursued, and Part 1 objectives were updated accordingly.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 8
- Model description
- This open-label, multi-center, phase Ib/II platform study design consisted of 3 parts. Part 1 was a phase Ib dose escalation and safety run-in for the 5 novel agents in combination with ruxolitinib to assess safety, tolerability and to confirm recommended Phase II dose. Parts 2 and 3 were phase II selection and expansion respectively, to assess preliminary efficacy of the combination treatments from Part 1 that were evaluated as safe and tolerable. The number of combination treatment arms opening in Part 2 depended on the results of Part 1. In Part 2, interim analysis was planned to determine if combination treatment(s) could be expanded in Part 3.
| Arm | Type | Receives |
|---|---|---|
| Part 1: Ruxolitinib + Siremadlin 20 mg | Experimental | Drug: Ruxolitinib, Drug: SiremadlinDose escalation of siremadlin added to existing stable dose of ruxolitinib |
| Part 1: Ruxolitinib + Siremadlin 30 mg | Experimental | Drug: Ruxolitinib, Drug: SiremadlinDose escalation of siremadlin added to existing stable dose of ruxolitinib |
| Part 1: Ruxolitinib + Siremadlin 40 mg | Experimental | Drug: Ruxolitinib, Drug: SiremadlinDose escalation of siremadlin added to existing stable dose of ruxolitinib |
| Part 1: Ruxolitinib + Rineterkib 200 mg | Experimental | Drug: Ruxolitinib, Drug: RineterkibDose escalation of rineterkib added to existing stable dose of ruxolitinib |
| Part 1: Ruxolitinib + Crizanlizumab | Experimental | Drug: Ruxolitinib, Drug: CrizanlizumabSafety run-in of crizanlizumab added to existing stable dose of ruxolitinib |
| Part 1: Ruxolitinib + Sabatolimab | Experimental | Drug: Ruxolitinib, Drug: SabatolimabSafety run-in of sabatolimab added to existing stable dose of ruxolitinib |
| Part 1: Ruxolitinib + NIS793 | Experimental | Drug: Ruxolitinib, Drug: NIS793Safety run-in of NIS793 added to existing stable dose of ruxolitinib |
| Part 2: Ruxolitinib | Active comparator | Drug: RuxolitinibExisting stable dose of ruxolitinib as control for Part 2 |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| RuxolitinibAlso: INC424, Jakavi5 mg tablets for oral use | Drug | Part 1: Ruxolitinib + Crizanlizumab, Part 1: Ruxolitinib + NIS793, Part 1: Ruxolitinib + Rineterkib 200 mg, Part 1: Ruxolitinib + Sabatolimab, Part 1: Ruxolitinib + Siremadlin 20 mg, Part 1: Ruxolitinib + Siremadlin 30 mg, Part 1: Ruxolitinib + Siremadlin 40 mg, Part 2: Ruxolitinib |
| SiremadlinAlso: HDM20110 mg, 20 mg, or 40 mg capsules for oral use | Drug | Part 1: Ruxolitinib + Siremadlin 20 mg, Part 1: Ruxolitinib + Siremadlin 30 mg, Part 1: Ruxolitinib + Siremadlin 40 mg |
| CrizanlizumabAlso: SEG101100 mg/10 mL concentrate for infusion for intravenous use | Drug | Part 1: Ruxolitinib + Crizanlizumab |
| SabatolimabAlso: MBG453100 mg/mL or 400 mg/4 mL concentrate for infusion for intravenous use | Drug | Part 1: Ruxolitinib + Sabatolimab |
| RineterkibAlso: LTT462100 mg capsule for oral use | Drug | Part 1: Ruxolitinib + Rineterkib 200 mg |
| NIS793700 mg/7 mL concentrate for infusion for intravenous use | Drug | Part 1: Ruxolitinib + NIS793 |
Primary outcome
Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1
Time frame: Baseline to the end of Cycle 2 (6 or 8 weeks)
Incidence and severity of dose limiting toxicities within the first 2 cycles (6 or 8 weeks) in Part 1 of the study. DLTs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria Version 5.0. Grade 0 was assigned for all non-missing values not graded as 1 or higher. Higher grade indicated more severity. Grade 5 was not used.
Response Rate at the End of Cycle 6 or Cycle 8 in Part 1
Time frame: Baseline to the end of Cycle 6 or 8 (24 weeks)
Composite of anemia improvement (hemoglobin level) and no spleen volume progression and no symptom worsening in Part 2 and Part 3 of the study. For a subject to be considered a responder, all three components of the composite had to be fulfilled.
18 secondary outcomes
Percentage of Subjects Achieving an Improvement in Hemoglobin Level of ≥ 1.5 g/dL From Baseline in Part 1
Time frame: Week 24, Week 48
Percentage of Subjects Achieving an Improvement in Hemoglobin Level of at Least >= 2.0 g/dL From Baseline in Part 1
Time frame: Week 24, Week 48
Change in Spleen Length From Baseline in Part 1
Time frame: Baseline, Week 24, Week 48
Percentage of Subjects With >=35% Reduction in Spleen Volume From Baseline in Part 1
Time frame: Week 24, Week 48
Percentage of Subjects With >=25% Reduction in Spleen Volume From Baseline in Part 1
Time frame: Week 24, Week 48
Percentage of Subjects in Part 1 With >=50% Reduction From Baseline in Myelofibrosis Symptom Assessment Form, Version 4.0 (MFSAF v4.0)
Time frame: Week 12, Week 24, Week 48
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1
Time frame: Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib
Area Under the Plasma Concentration Versus Time Curve From Time Zero to the Last Measurable Concentration Sampling Time (AUClast) for Ruxolitinib in Part 1
Time frame: Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1
Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1
Time frame: Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib
Maximum (Peak) Observed Plasma Drug Concentration (Cmax) for Ruxolitinib in Part 1
Time frame: Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1
Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Siremadlin, Rineterkib, Crizanlizumab, Sabatolimab, and NIS793 in Part 1
Time frame: Days 1 and 5 of Cycles 1 and 2 for siremadlin and Cycles 1 and 3 for crizanlizumab, sabatolimab, and NIS793; Days 1 and 15 of Cycle 1 for rineterkib
Time to Reach Maximum (Peak) Plasma, Blood, Serum or Other Body Fluid Drug Concentration After Single Dose Administration (Tmax) for Ruxolitinib in Part 1
Time frame: Days 1 and 5 of Cycles 1 and 2; Day 15 of Cycle 1
Concentration Versus Time Profile for Siremadlin in Part 1
Time frame: Day 1 of Cycles 1 and 2; Day 6 of Cycle 1; Days 2 and 5 of Cycles 1, 2, 3, 4, 5, and 6. Each cycle was 28 days.
Concentration Versus Time Profile for Rineterkib in Part 1
Time frame: Days 1, 2, 15, and 16 of Cycle 1; Day 1 of Cycles 2, 3, 4, 5, and 6. Each cycle was 28 days.
Concentration Versus Time Profile for Crizanlizumab in Part 1
Time frame: Days 1, 2, 8, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4, 5, 6, and 9. Each cycle was 28 days.
Concentration Versus Time Profile for Sabatolimab in Part 1
Time frame: Days 1, 2, 8, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4 and 5. Each cycle was 28 days.
Concentration Versus Time Profile for NIS793 in Part 1
Time frame: Days 1, 2, 4, 8, 11, and 15 of Cycles 1, 2, and 3; Day 1 of Cycles 4 and 5. Each cycle was 28 days.
Concentration Versus Time Profile for Ruxolitinib in Part 1
Time frame: Days 1, 2, 5, 6, and 15 of Cycles 1 and 2; Day 16 of Cycle 1; Days 1, 2, and 15 of Cycle 3; Days 1 and 5 of Cycles 4, 5, and 6. Each cycle was 28 days.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 40334082Ross DM, Heidel FH, Perkins AC, Reiter A, Crodel C, Riley C, Gomez-Casares MT, Takacs I, Becker H, Lehmann T, Vinogradova O, Burbury K, Vannucchi AM, Gupta V, Wondergem M, Kiladjian JJ, Cleary G, Zhang A, Kota J, Prahallad A, Wroclawska M, Lu M, Harrison CN. ADORE: an open platform study of ruxolitinib in combination with other novel therapies in patients with myelofibrosis. Blood Adv. 2025 Aug 26;9(16):4195-4205. doi: 10.1182/bloodadvances.2025015860.
- Individual participant dataSharing planned: Yes. Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.
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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.
Novartis Pharmaceuticals study director
Novartis Pharmaceuticals
22 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Ruxolitinib, Siremadlin and Crizanlizumab in people with Myelofibrosis, run by Novartis Pharmaceuticals at 22 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 7 Aug 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 sites in Germany, Spain, Australia, Switzerland, Canada and 8 more countries. 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 combined 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.
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 7 Aug 2025). 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?
Incidence and Severity of Dose Limiting Toxicities Within the First 2 Cycles in Part 1 (time frame: Baseline to the end of Cycle 2 (6 or 8 weeks)). The study lists 2 primary outcomes in all. 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 NCT04097821, 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 7 Aug 2025.