Selinexor in Myelofibrosis Refractory or Intolerant to JA... | NCT03627403

NCT03627403

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Sponsor/Collaborators Module

Name	Class
Karyopharm Therapeutics Inc	INDUSTRY

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Label	Type	Description	Intervention Names
Selinexor, all patients	Experimental	Single Arm Study, all patients will get selinexor	Drug: Selinexor

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Selinexor	Drug	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. For patients enrolled after Protocol v7, Selinexor will be administered by oral route beginning at 40mg once weekly. Prior to protocol version 7, the starting dose of sSelinexor was 60 mg and 80 mg once weekly.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Count of Participants With Reduction in Spleen Volume	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. This outcome will report the number of subjects with ≥ 35% reduction in spleen volume as measured by MRI or CT abdomen from baseline to after six cycles of treatment or end of treatment. Patients who did not complete six cycles of treatment received an MRI at discontinuation of therapy. Patients who died prior to completing six cycles of treatment or a follow-up scan were considered non-responders.	Up to 5.5 months

Secondary Outcomes

Measure	Description	Time Frame
Adverse Events That Occur	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. To evaluate the rate of adverse events (AEs) and serious adverse events (SAEs). This outcome measure will report the count of participants who experienced a Grade ≥ 3 AE while receiving study treatment until 30 days after the last dose of protocol treatment.

Eligibility Module

Eligibility 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 (≤ 28 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 indirect hyperbilirubinemia due to hemolysis or with Gilbert's syndrome where total bilirubin should be < 5 × ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 2.5 × ULN.
Renal (within 28 days prior to C1D1):
- Estimated creatinine clearance (CrCl) ≥ 20 mL/min using the Cockcroft and Gault formula [(140-Age) × Mass (kg)/(72 × creatinine mg/dL), multiply by 0.85 if the patient is female] OR
  - 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 v5.0 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.
Patients who are below their ideal body weight and would be unduly impacted by changes in their weight, in the opinion of the investigator, will be excluded
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 who are breastfeeding and unwilling to stop while on study

Contacts/Locations Module

Name	Affiliation	Role
Srinivas Tantravahi, MD	University of Utah	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Huntsman Cancer Institute/University of Utah		Salt Lake City	Utah	84112	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

Arm/Group Information

ID	Title	Description
FG000	Selinexor, All Patients	Single Arm Study, all patients received selinexor. Selinexor: Selinexor was administered weekly until IWG-MR disease progression, intolerable toxicity, or no clinical benefit per treating physician's discretion whichever occurs first. For patients enrolled after Protocol v7, Selinexor was administered by oral route beginning at 40mg once weekly. Prior to protocol version 7, the starting dose of Selinexor was 60 mg and 80 mg once weekly.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Selinexor, All Patients	Single Arm Study, all patients received selinexor. Selinexor: Selinexor was administered weekly until IWG-MR disease progression, intolerable toxicity, or no clinical benefit per treating physician's discretion whichever occurs first. For patients enrolled after Protocol v7, Selinexor was administered by oral route beginning at 40mg once weekly. Prior to protocol version 7, the starting dose of Selinexor was 60 mg and 80 mg once weekly.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Count of Participants With Reduction in Spleen Volume

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.

This outcome will report the number of subjects with ≥ 35% reduction in spleen volume as measured by MRI or CT abdomen from baseline to after six cycles of treatment or end of treatment. Patients who did not complete six cycles of treatment received an MRI at discontinuation of therapy. Patients who died prior to completing six cycles of treatment or a follow-up scan were considered non-responders.

Posted

Count of Participants

Participants

Up to 5.5 months

ID	Title	Description
OG000	Selinexor, All Patients	Single Arm Study, all patients received selinexor. Selinexor: Selinexor was administered weekly until IWG-MR disease progression, intolerable toxicity, or no clinical benefit per treating physician's discretion whichever occurs first. For patients enrolled after Protocol v7, Selinexor was administered by oral route beginning at 40mg once weekly. Prior to protocol version 7, the starting dose of Selinexor was 60 mg and 80 mg once weekly.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Selinexor, All Patients	Single Arm Study, all patients received selinexor. Selinexor: Selinexor was administered weekly until IWG-MR disease progression, intolerable toxicity, or no clinical benefit per treating physician's discretion whichever occurs first. For patients enrolled after Protocol v7, Selinexor was administered by oral route beginning at 40mg once weekly. Prior to protocol version 7, the starting dose of Selinexor was 60 mg and 80 mg once weekly. Participants experienced dose escalations and reductions based on their individual responses. Subjects were not assigned to fixed-dosing cohorts as dosing ranged from 20mg once weekly to 80 mg once weekly. Adverse Events were not collected specific to dose.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Acute kidney injury	Renal and urinary disorders		Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Abdominal distension	Gastrointestinal disorders		Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
IIT Data Management Team	Research Compliance Office, Huntsman Cancer Institute	801-213-6215		IITDataManagement@hci.utah.edu

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Mar 16, 2023	Aug 5, 2024	Prot_SAP_000.pdf
ICF	No	No	Yes	Informed Consent Form	Mar 16, 2023	Aug 5, 2024	ICF_001.pdf

Submission Tracking

Condition Browse Module

ID	Term
D055728	Primary Myelofibrosis

ID	Term
D009196	Myeloproliferative Disorders
D001855	Bone Marrow Diseases
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

Intervention Browse Module

ID	Term
C585161	selinexor

Masking Info

EG0001 events1 affected17 at risk

EG0004 events4 affected17 at risk