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Trial record 1 of 1 for:    A pilot study examining selinexor’s ability to overcome resistance in multiple myeloma patients who are refractory to lenalidomide-containing therapy.
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Selinexor Treatment for Multiple Myeloma Patients Who Are Refractory to Lenalidomide-containing Therapy.

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ClinicalTrials.gov Identifier: NCT04519476
Recruitment Status : Not yet recruiting
First Posted : August 19, 2020
Last Update Posted : October 27, 2020
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
Oncotherapeutics

Brief Summary:
This is a pilot study evaluating the safety and efficacy of selinexor among multiple myeloma (MM) patients that are refractory to lenalidomide-containing regimens with or without steroids.

Condition or disease Intervention/treatment Phase
Refractory Multiple Myeloma Drug: Selinexor Drug: Lenalidomide Drug: Methylprednisolone Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: A pilot study examining selinexor's ability to overcome resistance in multiple myeloma patients who are refractory to lenalidomide-containing therapy.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study Examining Selinexor's Ability to Overcome Resistance in Multiple Myeloma Patients Who Are Refractory to Lenalidomide-containing Therapy.
Estimated Study Start Date : November 1, 2020
Estimated Primary Completion Date : January 5, 2023
Estimated Study Completion Date : January 5, 2023

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arm Intervention/treatment
Experimental: Selinexor/Lenalidomide/Steroids
All subjects enrolled will receive: 1) selinexor, PO, at 60 mg once weekly on days 1-28 of a 28-day cycle, 2) lenalidomide, PO, 10 mg daily on days 1-21 of 28-days cycle and 3) methylprednisolone at the same dose and schedule as the last lenalidomide-containing regimen if it contained steroids. If patient's qualifying lenalidomide-containing regimen contained different type of steroid (e.g. prednisone, dexamethasone, etc.) then patient on this study will receive methylprednisolone at the equivalent dose and schedule.
Drug: Selinexor
Selinexor (KPT-330) is a first-in-class, oral selective exportin 1 (XPO1) inhibitor (1,2). Selinexor functions by binding with and inhibiting the nuclear export protein XPO1 (also called CRM1), leading to the accumulation of tumor suppressor proteins in the cell nucleus along with inhibition of translation of oncoprotein mRNAs.
Other Name: KPT-330

Drug: Lenalidomide
Immunomodulatory drug
Other Name: Revlimid

Drug: Methylprednisolone
Glucocorticoid, steroid
Other Name: Medrol




Primary Outcome Measures :
  1. Overall Response [ Time Frame: 30 months ]
    Overall Response Rate ([ORR]=CR +VGPR+ PR)

  2. Clinical Benefit Rate [ Time Frame: 30 months ]
    Clinical Benefit Rate ([CBR]= CR+VGPR+PR+MR)


Secondary Outcome Measures :
  1. Adverse Events Occurrences [ Time Frame: 30 months ]
    Occurrence of adverse events throughout the study, graded via CTCAE v.5.0

  2. Time to progression (TTP) [ Time Frame: 30 months ]
    defined as the time from the initiation of therapy to progressive disease

  3. Progression-free survival (PFS) [ Time Frame: 30 months ]
    defined as the time from initiation of therapy to progressive disease or death from any cause, whichever occurs first

  4. Time to first response [ Time Frame: 30 months ]
    defined as the time from the initiation of therapy to the first evidence of confirmed clinical benefit defined as > minimal response (MR, including patients who achieved a complete response (CR), very good partial response (VGPR), partial response (PR), or MR

  5. Duration of Response (DOR) [ Time Frame: 30 months ]
    defined as the time from the first response to progressive disease

  6. Overall survival (OS) [ Time Frame: 30 months ]
    defined as the time from initiation of therapy to death from any cause or last follow-up visit


Other Outcome Measures:
  1. Measuring levels of multiple myeloma specific biomarkers such as M-Protein and BCMA [ Time Frame: 30 months; duration of each cycle in this study is 28 days ]
    Levels will be measure on Day 1 Cycle 1 (baseline), Day 8 Cycle 1, Day 15 Cycle 1, Day 22 Cycle 1, and on Day 22 of every cycle thereafter. Duration of each cycle in this study is 28 days.



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

Inclusion Criteria:

  • Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:

    1. Age ≥ 18 year of age.
    2. Willing and able to provide written informed consent in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
    3. Able to adhere to the study visit schedule and other protocol requirements.
    4. ECOG Performance Status (PS) of ≤ 2.
    5. Has a diagnosis of MM based on standard criteria (9) as follows:

Major criteria:

  1. Plasmacytomas on tissue biopsy.
  2. Bone marrow plasmacytosis (greater than 30% plasma cells).
  3. Monoclonal immunoglobulin spike on serum electrophoresis IgG greater than 3.5 g/dL or IgA greater than 2.0 g/dL or kappa or lambda light chain excretion greater than 1 g/day on 24-hour urine protein electrophoresis.

Minor criteria:

  1. Bone marrow plasmacytosis (10% to 30% plasma cells).
  2. Monoclonal immunoglobulin present but of lesser magnitude than given under major criteria.
  3. Lytic bone lesions.
  4. Normal IgM less than 50 mg/dL, IgA less than 100 mg/dL, or IgG less than 600 mg/dL.

    Any of the following sets of criteria will confirm the diagnosis of multiple myeloma:

    • any 2 of the major criteria

    • major criterion 1 plus minor criterion 2, 3, or 4

    • major criterion 3 plus minor criterion 1 or 3

    • minor criteria 1, 2, and 3, or 1, 2, and 4

6. Currently has MM with measurable disease, defined as:

  • a monoclonal immunoglobulin spike on serum electrophoresis of at least 0.5 g/dL and/or
  • urine monoclonal protein levels of at least 200 mg/24 hours
  • for patients without measurable serum and urine M-protein levels, an involved SFLC > 100 mg/L or abnormal SFLC ratio 7. Currently has progressive MM: MM patients that are relapsed or have refractory disease from at least 3 regimens or lines of therapy are eligible for enrollment provided they fulfill the other eligibility criteria:
  • patients are considered relapsed, when they progress greater than 8 weeks from their last dose of treatment
  • patients are refractory when they progress while currently receiving the treatment or within 8 weeks of its last dose 8. Previous exposure to lenalidomide: failed lenalidomide (> 10 mg)-containing regimen (lenalidomide- containing regimen could be any prior regimen and is not required to be a part of their most recent treatment) and have received a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody therapy.

    9. Adequate hepatic function within 28 days prior to C1D1: Total bilirubin < 1.5 × upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of < 3 × ULN), and Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) normal to < 2 × ULN.

    10. Adequate renal function within 28 days prior to C1D1 as determined by serum creatinine of ≤1.5 mg/dL OR estimated CrCl of > 60 mL/min, calculated using the Cockcroft and Gault formula (140 - Age) • Mass (kg)/ (72 • creatinine mg/dL); multiply by 0.85 if female (10)(Appendix 5).

    11. Adequate hematopoietic function within 7 days prior to C1D1: total WBC count ≥1500/mm3, ANC ≥1000/mm3, hemoglobin ≥8.5 g/dL and platelet count ≥75,000/mm3 (patients for whom <50% of BM nucleated cells are plasma cells) or ≥50,000/mm3 (patients for whom ≥50% of BM nucleated cells are plasma cells).

    12. Patients receiving hematopoietic growth factor support, including erythropoietin, darbepoetin, G-CSF, GM-CSF, and platelet stimulators (e.g., eltrombopag, romiplostim, or interleukin-11) must have a 2-week interval between growth factor support and the Screening assessments, but they may receive growth factor support during the study.

    13. Patients must have:

  • At least a 2-week interval from the last red blood cell (RBC) transfusion prior to the start of study treatment
  • At least a 1-week interval from the last platelet transfusion prior to the start of study treatment
  • However, patients may receive RBC and/or platelet transfusions as clinically indicated per institutional guidelines during the study 14. Patients must be registered into the mandatory REVLIMID REMS™ program and be willing and able to comply with the requirements of the REVLIMID REMS™ program.

    15. Female patients of childbearing potential (FCBP) must have a negative serum pregnancy test at Screening. Female patients of childbearing potential and fertile male patients who are sexually active with a female of childbearing potential must use highly effective methods of contraception throughout the study and for 3 months following the last dose of study treatment, specifically:

  • FCBP† must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of starting treatment and must either commit to continued abstinence from heterosexual intercourse or use acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, and at least 28 days before she starts therapy. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of every 28 days about pregnancy precautions and risks of fetal exposure.

    • A FCBP (female of childbearing potential) is a sexually mature woman who: 1) has not undergone a hysterectomy or bilateral oophorectomy; or 2) has not been naturally postmenopausal for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months) Able to take aspirin (acetylsalicylic acid, ASA) at 81 or 325 mg/daily as antiplatelet therapy if platelet count is above 30 x 109/L (subjects intolerant to ASA may use warfarin or low molecular weight heparin)

Exclusion Criteria:

  • Patients meeting any of the following exclusion criteria are not eligible to enroll in this study:

    1. Has received selinexor or another XPO1 inhibitor previously.
    2. Prior malignancy that required treatment or has shown evidence of recurrence (except for non-melanoma skin cancer or adequately treated cervical carcinoma in situ) during the 5 years prior to randomization. Cancer treated with curative intent for >5 years previously and without evidence of recurrence will be allowed.
    3. Has any concurrent medical condition or disease (e.g., uncontrolled active hypertension, uncontrolled active diabetes, active systemic infection, POEMS syndrome [polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes], primary amyloidosis, etc.) that is likely to interfere with study procedures.
    4. Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within 1 week prior to Cycle 1 Day 1 (C1D1). Patients on prophylactic antibiotics or with a controlled infection within 1 week prior to C1D1 are acceptable.
    5. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
    6. Known hypersensitivity to compounds of similar chemical or biological composition to thalidomide and lenalidomide or steroids.
    7. Concurrent use of other anti-cancer agents or treatments.
    8. The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
    9. Severe hypercalcemia, i.e., serum calcium ≥ 12 mg/dL (3.0 mmol/L) corrected for albumin
    10. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study.
    11. Pregnant or breastfeeding females.
    12. BSA <1.4 m2 at baseline, calculated by the Dubois (58) or Mosteller (59) method.
    13. Life expectancy of less than 3 months.
    14. Major surgery within 4 weeks prior to C1D1.
    15. Active, unstable cardiovascular function, as indicated by the presence of:

    1. Symptomatic ischemia, or 2. Uncontrolled clinically significant conduction abnormalities (e.g., patients with ventricular tachycardia on anti-arrhythmic are excluded; patients with first degree atrioventricular block or asymptomatic left anterior fascicular block/right bundle branch block will not be excluded), or 3. CHF of New York Heart Association Class ≥3 or known left ventricular ejection fraction < 40%, or 4. MI within 3 months prior to C1D1. 16. Known active HIV infection or HIV seropositivity. 17. 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.

    18. Any active GI dysfunction interfering with the patient's ability to swallow tablets, or any active GI dysfunction that could interfere with absorption of study treatment.

    19. Inability or unwillingness to take supportive medications such as anti-nausea and anti-anorexia agents as recommended by the National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology (CPGO) (NCCN CPGO) for antiemesis and anorexia/cachexia (palliative care).

    20. Any active, serious psychiatric, medical, or other conditions/situations that, in the opinion of the Investigator, could interfere with treatment, compliance, or the ability to give informed consent.

    21. Contraindication to any of the required concomitant drugs or supportive treatments.

    22. Patients unwilling or unable to comply with the protocol.


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): NCT04519476


Contacts
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Contact: Noemi Silagan, MD (310)623-1204 NSilagan@oncotherapeutics.com
Contact: Tanya Spektor, PhD (323)251-5941 tspektor@oncotherapeutics.com

Locations
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United States, California
James R Berenson, MD, Inc.
West Hollywood, California, United States, 90069
Contact: James Berenson, MD         
Contact: Regina Swift, RN, BSN    310-623-1222    rswift@berensononcology.com   
Sponsors and Collaborators
Oncotherapeutics
Karyopharm Therapeutics Inc
Investigators
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Principal Investigator: James R Berenson, MD Oncotherapeutics
Publications:
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Responsible Party: Oncotherapeutics
ClinicalTrials.gov Identifier: NCT04519476    
Other Study ID Numbers: IST-321
First Posted: August 19, 2020    Key Record Dates
Last Update Posted: October 27, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We will share overall demographics of the study population, clinical responses, AEs and SAEs.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Oncotherapeutics:
Selinexor
Lenalidomide-Refractory
Multiple Myeloma
Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Lenalidomide
Prednisolone hemisuccinate
Prednisolone phosphate
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Anti-Inflammatory Agents