Fostamatinib as a Single Agent or in Combination With Ruxolitinib for Treatment of Patients With Myelofibrosis With Severe Thrombocytopenia

Sponsor
Washington University School of Medicine (Other)
Overall Status
Recruiting
CT.gov ID
NCT04543279
Collaborator
Rigel Pharmaceuticals (Industry)
12
1
2
36.9
0.3

Study Details

Study Description

Brief 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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Anticipated Enrollment :
12 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Fostamatinib as a Single Agent or in Combination With Ruxolitinib for Treatment of Patients With Myelofibrosis With Severe Thrombocytopenia
Actual Study Start Date :
May 3, 2021
Anticipated Primary Completion Date :
May 31, 2024
Anticipated Study Completion Date :
May 31, 2024

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part A: Fostamatinib

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.

Drug: Fostamatinib
Fostamatinib will be supplied by Rigel Pharmaceuticals.
Other Names:
  • Tavalisse
  • Experimental: Part B: Fostamatinib + Ruxolitinib

    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.

    Drug: Fostamatinib
    Fostamatinib will be supplied by Rigel Pharmaceuticals.
    Other Names:
  • Tavalisse
  • Drug: Ruxolitinib
    Ruxolitinib is commercially available.
    Other Names:
  • Jakafi
  • Outcome Measures

    Primary Outcome Measures

    1. Platelet response (Part A) [Through 12 weeks]

      -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

    2. Toxicity of fostamatinib and ruxolitinib treatment (Part B) [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

    Secondary Outcome Measures

    1. Number of participants eligible to initiate therapy with ruxolitinib (Part A) [Through completion of fostamatinib treatment (12 weeks)]

    2. Toxicity of fostamatinib treatment (Part A) [From start of treatment through 30 days after last day of study treatment (estimated to be approximately 16 weeks)]

      -Measured by number of adverse events, serious adverse events, and laboratory abnormalities

    3. Number of participants who permanently discontinue fostamatinib due to fostamatinib related adverse events(Part A) [Through 12 weeks]

    4. Number of participants who require treatment interruption of fostamatinib due to adverse events (Part A) [Through 12 weeks]

    5. Number of participants who was dose escalated and tolerated fostamatinib dose greater than 100 mg BID (Part A) [Through 12 weeks]

    6. Number of participants who achieve 35% or greater reduction in spleen volume as determined by ultrasound at week 12 of fostamatinib treatment (Part A) [Week 12]

    7. Mean reduction is spleen volume as determined by ultrasound at week 12 of fostamatinib treatment (Part A) [Week 12]

    8. Number of participants with 50% or greater improvement in Total Symptom Score (Part A) [Week 12]

    9. Number of participants who achieve platelet transfusion independence (Part A) [Through week 12]

    10. Number of participants with anemia who achieve RBC transfusion independence (Part A) [Through week 12]

    11. Change in marrow fibrosis by WHO grading (Part A) [Through week 12]

    12. Number of participants with 35% or greater reduction in spleen volume as determined by ultrasound after 12 weeks of combination treatment (Part B) [12 weeks]

    13. Number of participants with 35% or greater reduction in spleen volume as determined by ultrasound after 12 weeks of combination treatment (Part B) [At completion of combination treatment (estimated to be 36 weeks)]

    14. Mean reduction in spleen volume as determined by ultrasound after 12 weeks of combination treatment (Part B) [12 weeks]

    15. Mean reduction in spleen volume as determined by ultrasound after 12 weeks of combination treatment (Part B) [At completion of combination treatment (estimated to be 36 weeks)]

    16. Number of participants with 50% or greater improvement in Total Symptom Score (Part B) [12 weeks]

    17. Number of participants with 50% or greater improvement in Total Symptom Score (Part B) [At completion of combination treatment (estimated to be 36 weeks)]

    18. Duration of uninterrupted ruxolitinib treatment (Part B) [Up to 36 weeks]

    19. Change in marrow fibrosis by WHO grading (Part B) [At completion of combination treatment (estimated to be 36 weeks)]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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:

    • 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).

    Exclusion Criteria:
    • 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.

    • 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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Washington University School of Medicine Saint Louis Missouri United States 63110

    Sponsors and Collaborators

    • Washington University School of Medicine
    • Rigel Pharmaceuticals

    Investigators

    • Principal Investigator: Amy Zhou, M.D., Washington University School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Washington University School of Medicine
    ClinicalTrials.gov Identifier:
    NCT04543279
    Other Study ID Numbers:
    • 202011080
    First Posted:
    Sep 10, 2020
    Last Update Posted:
    May 9, 2022
    Last Verified:
    May 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of May 9, 2022