Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 29 for:    Myelofibrosis | Utah, United States
Previous Study | Return to List | Next Study

Selinexor in Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors (ESSENTIAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03627403
Recruitment Status : Recruiting
First Posted : August 13, 2018
Last Update Posted : January 28, 2020
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
University of Utah

Brief Summary:
This is a phase II, open label, prospective, single-arm study evaluating the efficacy and safety of selinexor in patients with PMF or secondary MF (PPV-MF or PET-MF) who are refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors.

Condition or disease Intervention/treatment Phase
Primary Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Post-polycythemia Vera Myelofibrosis Drug: Selinexor Phase 2

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open label, non-randomized, prospective, single-arm study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study to Evaluate the Efficacy and Safety of Selinexor in Patients With Myelofibrosis Refractory or Intolerant to JAK1/2 Inhibitors
Actual Study Start Date : March 14, 2019
Estimated Primary Completion Date : March 14, 2024
Estimated Study Completion Date : March 14, 2025


Arm Intervention/treatment
Experimental: Selinexor, all patients
Single Arm Study, all patients will get selinexor
Drug: Selinexor
Selinexor will be administered orally at a dose of 80 mg once weekly until IWG-MR disease progression, intolerable toxicity, or no clinical benefit per treating physician's discretion whichever occurs first.




Primary Outcome Measures :
  1. Change in spleen volume [ Time Frame: Up to 6 months ]

    To assess the efficacy of selinexor on spleen volume reduction in subjects with myelofibrosis (PMF, PET-MF, or PPV-MF) refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors.

    Change and percentage change in spleen volume from baseline to EOT as measured by MRI or CT (in applicable patients).



Secondary Outcome Measures :
  1. Adverse Events that Occur [ Time Frame: Up to 6 months ]

    To assess the safety/tolerability and further characterize the safety profile of selinexor in PMF, PET-MF, or PPV-MF patients refractory or intolerant to ruxolitinib and/or any other experimental JAK1/2 inhibitors.

    Secondary Endpoints: rate of adverse events (AEs) and serious adverse events (SAEs).


  2. Change in symptoms score [ Time Frame: Up to 6 months ]

    Proportion of patients with ≥ 50% reduction of total symptoms score as measured by the MPN-Symptoms Assessment Form (MPN-SAF) from baseline to cycle 7 day 1.

    The score will be reported as one mean score of all of the questions in the questionnaire. The higher the score, the worse the symptom.


  3. Overall response [ Time Frame: Up to 6 months ]
    Overall response rate according to the 2013 IWG-MRT consensus criteria for treatment response in primary and secondary MF (post-PV and post-ET).

  4. Overall Survival [ Time Frame: Up to 24 months ]
    Overall survival from the initiation of study therapy to 24 months.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subject aged ≥ 18 years.
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Diagnosis of primary myelofibrosis (PMF), post-essential thrombocytosis (PET-MF) or post-polycythemia vera (PPV-MF).
  • Life expectancy ≥ 6 months.
  • Prior treatment with ruxolitinib or any experimental JAK1/2 inhibitor with any one or more of the following:

    a. Inadequate response after being on ≥ 3 months of treatment defined by: i. Palpable spleen ≥ 10 cm below the left subcostal margin on physical examination at the screening visit OR ii. Palpable spleen ≥ 5cm below the left subcostal margin on physical examination at the screening visit AND active symptoms of MF at the screening visit defined presence of 1 symptom score of ≥ 5 or two symptom scores each of ≥ 3 using the Screening Symptoms Form (Appendix 6) b. Intolerant to ruxolitinib and/or other JAK1/2 inhibitors due to any grade ≥ 3 non-hematologic AEs of or any grade ≥ 2 AEs requiring treatment discontinuation AND palpable spleen ≥ 5cm below the left subcostal margin on physical examination at the screening visit.

  • Adequate organ function as defined as:

    • Hematologic (≤ 7 days prior to C1D1):

      • Total white blood cell (WBC) count ≥ 1000/mm3
      • Absolute neutrophil count (ANC) ≥ 500/mm3
      • Hemoglobin ≥ 7 g/dL
      • Platelet count ≥ 30,000/mm3

For patients receiving transfusion and growth factor support, the following delays must be observed between the last administration and hematologic laboratory screening assessments:

• For hematopoietic growth factor support (including erythropoietin, darbepoetin, granulocyte-colony stimulating factor [G-CSF], granulocyte macrophage-colony stimulating factor [GM-CSF], and platelet stimulators [e.g., eltrombopag, romiplostim, or interleukin-11]): at least 2 weeks.

Growth factor support, RBC and/or platelet transfusions are allowed as clinically indicated per institutional guidelines during the study.

  • Hepatic (≤ 28 days prior to C1D1):

    • Total bilirubin < 1.5 × ULN except in patients with Gilbert's syndrome who must have a total bilirubin < 3 × ULN
    • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2 × ULN.
  • Renal (within 28 days prior to C1D1):

    • Estimated creatinine clearance (CrCl) ≥ 20 mL/min using the Cockroft and Gault formula [(140-Age) × Mass (kg)/(72 × creatinine mg/dL), multiply by 0.85 if the patient is female] OR
    • Measured CrCl ≥ 20 mL/min by 24-hour urine collection.

      • Female patients of childbearing potential must have a negative serum pregnancy test (≤ 3 days prior to C1D1).
      • Female patients of childbearing potential must agree to use 2 methods of contraception throughout the study and for 3 months following the last dose of study treatment (including 1 highly effective and 1 effective method of contraception as defined in section 7.4)
      • Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential.
      • Recovery to baseline or ≤ Grade 1 CTCAE v5.04 from toxicities related to any prior treatments including ruxolitinib or other experimental agents, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
      • Able to provide informed consent and willing to sign an approved consent form that conforms to federal and institutional guidelines.

Exclusion Criteria:

  • Prior exposure to a SINE compound, including selinexor.
  • BSA < 1.4 m2 at baseline, calculated by the Dubois or Mosteller methods.
  • Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals ≤ 1 week prior to C1D1. Patients on prophylactic antibiotics or with a controlled infection ≤ 1 week prior to C1D1 are acceptable.
  • Radiation, chemotherapy, immunotherapy, or any other anticancer therapy (including investigational therapies) ≤ 2 weeks.
  • Ruxolitinib or other JAK1/2 inhibitors ≤ at least 3 days or 5 half-lives prior to C1D1.
  • Major surgery ≤ 4 weeks prior to C1D1.
  • Known active hepatitis A, B, or C infection; or known to be positive for hepatitis C virus ribonucleic acid (RNA) or hepatitis B virus surface antigen.
  • Any active gastrointestinal dysfunction interfering with the patient's ability to swallow tablets, or any active gastrointestinal dysfunction that could interfere with absorption of study treatment.
  • Any life-threatening illness, organ system dysfunction, or serious psychiatric, medical, or other conditions/situations which, in the investigator's opinion, could compromise a patient's ability to give informed consent, safety, or compliance with the protocol.
  • Contraindication to any of the required concomitant drugs or supportive treatments.
  • Subjects taking prohibited medications as described in Section 6.3. Following discontinuation of prohibited medications, a washout period is required prior to initiating study treatment (the duration of the washout must be as clinically indicated, e.g. at least five half-lives).
  • Subjects with circulating lymphocytes > 50,000/mm3 (50 G/L)
  • Subjects who are breastfeeding and unwilling to stop while on study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03627403


Contacts
Layout table for location contacts
Contact: Priscilla Blosser, RN 801-213-6117 Priscilla.blosser@hci.utah.edu

Locations
Layout table for location information
United States, Utah
Huntsman Cancer Institute/University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Priscilla Blosser, RN    801-213-6117    Priscilla.blosser@hci.utah.edu   
Sponsors and Collaborators
University of Utah
Karyopharm Therapeutics Inc
Investigators
Layout table for investigator information
Principal Investigator: Srinivas Tantravahi, MD University of Utah

Layout table for additonal information
Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT03627403    
Other Study ID Numbers: HCI114354
First Posted: August 13, 2018    Key Record Dates
Last Update Posted: January 28, 2020
Last Verified: January 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Primary Myelofibrosis
Polycythemia Vera
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders