MyelofibrosisPhase 2NCT04543279
Fostamatinib as a Single Agent or in Combination With Ruxolitinib for Treatment of Patients With Myelofibrosis With Severe Thrombocytopenia
A Phase 2 study testing Fostamatinib and Ruxolitinib in people with Myelofibrosis and Thrombocytopenia, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Fostamatinib may improve thrombocytopenia in myelofibrosis patients with severe thrombocytopenia (platelet <50,000/microL) and allow them to initiate treatment with a JAK2 inhibitor, ruxolitinib. Additionally, fostamatinib monotherapy may also improve myelofibrosis related symptoms and splenomegaly. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelofibrosis, Thrombocytopenia
- What is being tested?
- Fostamatinib and Ruxolitinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 3 May 2021to 30 Jul 2022
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of primary myelofibrosis or post-polycythemia vera/essential thrombocythemia myelofibrosis classified as high risk, intermediate-2 risk, or intermediate 1 risk by IPSS.
- Severe thrombocytopenia defined as platelet count < 50,000/microL (confirmed on at least two measurements over an 8-week period prior to start of study).
- At least 18 years of age.
- ECOG performance status ≤ 2
- Able to swallow pills
- Adequate bone marrow and organ function as defined below:
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- ANC ≥ 1000/microL
- Peripheral blood blasts ≤ 10%
- Albumin > 2.7 g/dL
- Total bilirubin ≤ 1.5 x IULN; patients with Gilbert's syndrome may enroll if direct bilirubin ≤ 1.5 x IULN
- AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN
- Creatinine clearance > 30 mL/min by Cockcroft-Gault
- Female subjects must be either post-menopausal for at least 1 year or surgically sterile; or, if of childbearing potential, must not be pregnant or lactating and must agree to use a highly effective method of birth control throughout the duration of the trial and for 30 days following the last dose. Acceptable methods of birth control are defined as: hormonal contraception (pill, injection or implant) used consistently for at least 30 days prior to screening, an intrauterine device (IUD), or intrauterine hormone-releasing system (IUS), or true abstinence (i.e. abstinence is in line with the preferred and usual lifestyle of the subject.). Male subjects do not need to use contraception for fostamatinib because human studies showed minimal R406 in sperm.
- Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Who cannot join
- History of allogeneic stem cell transplant.
- Any solid tumor or hematologic malignancy (other than myelofibrosis) requiring active treatment at the time of study entry
- Currently receiving any other investigational agents.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to fostamatinib, ruxolitinib, or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, or cardiac arrhythmia.
- Subject has uncontrolled or poorly controlled hypertension, defined as systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥80 mmHg, whether or not the subject is receiving anti-hypertensive treatment.
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- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 14 days of study entry and prior to the first dose of fostamatinib.
- Known positive status for human immunodeficiency virus (HIV)
- Chronic, active, or acute viral hepatitis A, B, or C infection, or hepatitis B or C carrier.
- Treatment with strong CYP3A inhibitors or inducers within 14 days before the first dose of study drug. Strong CYP3A inhibitors and CYP3A inducers are not permitted during the study.
- Ongoing gastrointestinal medical condition such as Crohn's disease, inflammatory bowel disease, or chronic diarrhea that is not well controlled and could interfere with absorption of oral medication or be exacerbated by study medication
- Known hepatic cirrhosis or severe pre-existing hepatic impairment.
- Uncontrolled coagulopathy or bleeding disorder.
- Female patients who intend to donate eggs and male patients who intend to donate sperm during the course of this study or for 4 months after receiving the last dose of study treatment.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Fostamatinib may improve thrombocytopenia in myelofibrosis patients with severe thrombocytopenia (platelet <50,000/microL) and allow them to initiate treatment with a JAK2 inhibitor, ruxolitinib. Additionally, fostamatinib monotherapy may also improve myelofibrosis related symptoms and splenomegaly.
- Conditions
- Myelofibrosis, Thrombocytopenia
- Being tested
- Fostamatinib, Ruxolitinib
- Medical subject headings
- Primary Myelofibrosis, Thrombocytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FostamatinibDrug
Also called Tavalisse
Fostamatinib will be supplied by Rigel Pharmaceuticals.
RuxolitinibDrug
Also called Jakafi
Ruxolitinib is commercially available.
| Study group | Role | What they receive |
|---|---|---|
| Part A: Fostamatinib | Experimental | The starting dose of fostamatinib is 100 mg twice daily (BID). After the first cycle, if no major dose related safety issue is observed and the platelet count is less than 50K/microL, then the fostamatinib dose will be increased to 150 mg BID for the next 2 cycles; otherwise the dose may be continued at 100 mg BID. Receives: Drug: Fostamatinib |
| Part B: Fostamatinib + Ruxolitinib | Experimental | After 3 cycles of fostamatinib monotherapy, all patients with a sustained platelet count ≥ 50K/microL, will continue on the current fostamatinib dose plus ruxolitinib at the recommended dose per standard prescribing guidelines for an additional 9 cycles.
Patients who do not reach platelet count of at least 50K/microL but who achieve clinical benefit per the treating provider may continue on single agent fostamatinib for up to 12 total treatment cycles. If these patients achieve a sustained platelet count of ≥ 50K/microL at any point prior to Cycle 10 Day 1, then they may be eligible to enroll in Part B of the study and continue treatment with fostamatinib and ruxolitinib for the remainder of the study. Receives: Drug: Fostamatinib; Drug: Ruxolitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With a Platelet Response (Part A)
-Defined as an increase in platelet count ≥ 50K/microL with at least one more confirmatory platelet count separated by at least 2 weeks (in the absence of platelet transfusion) within the first 12 weeks of fostamatinib treatment
Measured: Week 12
Toxicity of Fostamatinib and Ruxolitinib Treatment (Part B)
-Measured by number of adverse events, serious adverse events, and laboratory abnormalities
Measured: From start of treatment through 30 days after last day of study treatment (estimated to be approximately 40 weeks)
Secondary outcomes (19)
Number of Participants Eligible to Initiate Therapy With Ruxolitinib (Part A)
Measured: Through completion of fostamatinib treatment (12 weeks)
Toxicity of Fostamatinib Treatment (Part A)
-Measured by number of adverse events, serious adverse events, and laboratory abnormalities
Measured: From start of treatment through 30 days after last day of study treatment (estimated to be approximately 16 weeks)
Number of Participants Who Permanently Discontinue Fostamatinib Due to Fostamatinib Related Adverse Events (Part A)
Measured: Through 12 weeks
Number of Participants Who Require Treatment Interruption of Fostamatinib Due to Adverse Events (Part A)
Measured: Through 12 weeks
Number of Participants Who Was Dose Escalated and Tolerated Fostamatinib Dose Greater Than 100 mg BID (Part A)
Measured: Through 12 weeks
Number of Participants Who Achieve 35% or Greater Reduction in Spleen Volume as Determined by Ultrasound at Week 12 of Fostamatinib Treatment (Part A)
Measured: Week 12
Change in Mean Spleen Volume as Determined by Ultrasound at Week 12 of Fostamatinib Treatment (Part A)
Measured: Week 12
Number of Participants With 50% or Greater Improvement in Myeloproliferative Neoplasm - Symptom Assessment Form Total Symptom Score (Part A) From Baseline to Week 12
-The Myeloproliferative Neoplasm - Symptom Assessment Form Total Symptom Score (MPN-SAF-TSS) has 10 questions for participants to rate their symptoms. The answers range from 0-absent to 10-worst imaginable. The total score for the questionnaire is 100. A higher score indicates worse symptoms.
Measured: Baseline and Week 12
Number of Participants Who Achieve Platelet Transfusion Independence (Part A)
Measured: Through week 12
Number of Participants With Anemia Who Achieve RBC Transfusion Independence (Part A)
Measured: Through week 12
Number of Participants With Change in Marrow Fibrosis by WHO Grading (Part A)
Measured: Through week 12
Number of Participants With 35% or Greater Reduction in Spleen Volume as Determined by Ultrasound After 12 Weeks of Combination Treatment (Part B)
Measured: 12 weeks
Number of Participants With 35% or Greater Reduction in Spleen Volume as Determined by Ultrasound After 12 Weeks of Combination Treatment (Part B)
Measured: At completion of combination treatment (estimated to be 36 weeks)
Mean Reduction in Spleen Volume as Determined by Ultrasound After 12 Weeks of Combination Treatment (Part B)
Measured: 12 weeks
Mean Reduction in Spleen Volume as Determined by Ultrasound After 12 Weeks of Combination Treatment (Part B)
Measured: At completion of combination treatment (estimated to be 36 weeks)
Number of Participants With 50% or Greater Improvement in Total Symptom Score (Part B)
Measured: 12 weeks
Number of Participants With 50% or Greater Improvement in Total Symptom Score (Part B)
Measured: At completion of combination treatment (estimated to be 36 weeks)
Duration of Uninterrupted Ruxolitinib Treatment (Part B)
Measured: Up to 36 weeks
Change in Marrow Fibrosis by WHO Grading (Part B)
Measured: At completion of combination treatment (estimated to be 36 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2020
- Study start3 May 2021
- Primary completion1 Jul 2022
- Study completion30 Jul 2022
Why it stopped: Low accrual
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.
- Other trials for MyelofibrosisStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Rigel Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Amy Zhou, M.D., Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04543279
- Sponsor's protocol ID
- 202011080
- Status last verified
- Dec 2023
- First submitted
- 8 Sep 2020
- Last updated
- 15 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fostamatinib as a Single Agent or in Combination With Ruxolitinib for Treatment of Patients With Myelofibrosis With Severe Thrombocytopenia
- ClinicalTrials.gov ID
- NCT04543279
- Acronym / sponsor ID
- 202011080
- Conditions
- Myelofibrosis, Thrombocytopenia
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Collaborators
- Rigel Pharmaceuticals
- Study start
- 3 May 2021 (actual)
- Primary completion
- 1 Jul 2022 (actual)
- Study completion
- 30 Jul 2022 (actual)
- First posted
- 10 Sep 2020 (actual)
- Results
- Posted 15 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Fostamatinib may improve thrombocytopenia in myelofibrosis patients with severe thrombocytopenia (platelet <50,000/microL) and allow them to initiate treatment with a JAK2 inhibitor, ruxolitinib. Additionally, fostamatinib monotherapy may also improve myelofibrosis related symptoms and splenomegaly.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part A: Fostamatinib | Experimental | Drug: FostamatinibThe starting dose of fostamatinib is 100 mg twice daily (BID). After the first cycle, if no major dose related safety issue is observed and the platelet count is less than 50K/microL, then the fostamatinib dose will be increased to 150 mg BID for the next 2 cycles; otherwise the dose may be continued at 100 mg BID. |
| Part B: Fostamatinib + Ruxolitinib | Experimental | Drug: Fostamatinib, Drug: RuxolitinibAfter 3 cycles of fostamatinib monotherapy, all patients with a sustained platelet count ≥ 50K/microL, will continue on the current fostamatinib dose plus ruxolitinib at the recommended dose per standard prescribing guidelines for an additional 9 cycles. Patients who do not reach platelet count of at least 50K/microL but who achieve clinical benefit per the treating provider may continue on single agent fostamatinib for up to 12 total treatment cycles. If these patients achieve a sustained platelet count of ≥ 50K/microL at any point prior to Cycle 10 Day 1, then they may be eligible to enroll in Part B of the study and continue treatment with fostamatinib and ruxolitinib for the remainder of the study. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Confirmed diagnosis of primary myelofibrosis or post-polycythemia vera/essential thrombocythemia myelofibrosis classified as high risk, intermediate-2 risk, or intermediate 1 risk by IPSS.
- Severe thrombocytopenia defined as platelet count < 50,000/microL (confirmed on at least two measurements over an 8-week period prior to start of study).
- At least 18 years of age.
- ECOG performance status ≤ 2
- Able to swallow pills
Key exclusion criteria (14 listed)
- History of allogeneic stem cell transplant.
- Any solid tumor or hematologic malignancy (other than myelofibrosis) requiring active treatment at the time of study entry
- Currently receiving any other investigational agents.
- A history of allergic reactions attributed to compounds of similar chemical or biologic composition to fostamatinib, ruxolitinib, or other agents used in the study.
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, or cardiac arrhythmia.
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 |
|---|---|---|
| FostamatinibAlso: TavalisseFostamatinib will be supplied by Rigel Pharmaceuticals. | Drug | Part A: Fostamatinib, Part B: Fostamatinib + Ruxolitinib |
| RuxolitinibAlso: JakafiRuxolitinib is commercially available. | Drug | Part B: Fostamatinib + Ruxolitinib |
Primary outcome
Number of Participants With a Platelet Response (Part A)
Time frame: Week 12
-Defined as an increase in platelet count ≥ 50K/microL with at least one more confirmatory platelet count separated by at least 2 weeks (in the absence of platelet transfusion) within the first 12 weeks of fostamatinib treatment
Toxicity of Fostamatinib and Ruxolitinib Treatment (Part B)
Time frame: From start of treatment through 30 days after last day of study treatment (estimated to be approximately 40 weeks)
-Measured by number of adverse events, serious adverse events, and laboratory abnormalities
19 secondary outcomes
Number of Participants Eligible to Initiate Therapy With Ruxolitinib (Part A)
Time frame: Through completion of fostamatinib treatment (12 weeks)
Toxicity of Fostamatinib Treatment (Part A)
Time frame: From start of treatment through 30 days after last day of study treatment (estimated to be approximately 16 weeks)
Number of Participants Who Permanently Discontinue Fostamatinib Due to Fostamatinib Related Adverse Events (Part A)
Time frame: Through 12 weeks
Number of Participants Who Require Treatment Interruption of Fostamatinib Due to Adverse Events (Part A)
Time frame: Through 12 weeks
Number of Participants Who Was Dose Escalated and Tolerated Fostamatinib Dose Greater Than 100 mg BID (Part A)
Time frame: Through 12 weeks
Number of Participants Who Achieve 35% or Greater Reduction in Spleen Volume as Determined by Ultrasound at Week 12 of Fostamatinib Treatment (Part A)
Time frame: Week 12
Change in Mean Spleen Volume as Determined by Ultrasound at Week 12 of Fostamatinib Treatment (Part A)
Time frame: Week 12
Number of Participants With 50% or Greater Improvement in Myeloproliferative Neoplasm - Symptom Assessment Form Total Symptom Score (Part A) From Baseline to Week 12
Time frame: Baseline and Week 12
Number of Participants Who Achieve Platelet Transfusion Independence (Part A)
Time frame: Through week 12
Number of Participants With Anemia Who Achieve RBC Transfusion Independence (Part A)
Time frame: Through week 12
Number of Participants With Change in Marrow Fibrosis by WHO Grading (Part A)
Time frame: Through week 12
Number of Participants With 35% or Greater Reduction in Spleen Volume as Determined by Ultrasound After 12 Weeks of Combination Treatment (Part B)
Time frame: 12 weeks
Number of Participants With 35% or Greater Reduction in Spleen Volume as Determined by Ultrasound After 12 Weeks of Combination Treatment (Part B)
Time frame: At completion of combination treatment (estimated to be 36 weeks)
Mean Reduction in Spleen Volume as Determined by Ultrasound After 12 Weeks of Combination Treatment (Part B)
Time frame: 12 weeks
Mean Reduction in Spleen Volume as Determined by Ultrasound After 12 Weeks of Combination Treatment (Part B)
Time frame: At completion of combination treatment (estimated to be 36 weeks)
Number of Participants With 50% or Greater Improvement in Total Symptom Score (Part B)
Time frame: 12 weeks
Number of Participants With 50% or Greater Improvement in Total Symptom Score (Part B)
Time frame: At completion of combination treatment (estimated to be 36 weeks)
Duration of Uninterrupted Ruxolitinib Treatment (Part B)
Time frame: Up to 36 weeks
Change in Marrow Fibrosis by WHO Grading (Part B)
Time frame: At completion of combination treatment (estimated to be 36 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of MedicineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Amy Zhou, M.D. principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fostamatinib and Ruxolitinib in people with Myelofibrosis and Thrombocytopenia, run by Washington University School of Medicine 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 14 inclusion and 14 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 15 Dec 2023. 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 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 15 Dec 2023). 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?
Number of Participants With a Platelet Response (Part A) (time frame: Week 12). 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?
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 15 Dec 2023.