SELIBORDARA: Selinexor, Bortezomib and Daratumumab in Multiple Myeloma

NCT ID: NCT03589222

Last Updated: 2021-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

62 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-15

Study Completion Date

2023-08-31

Brief Summary

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Phase 2, single-arm, open, non-randomized, multicenter study of the SINE™ compound selinexor plus low-dose dexamethasone, in combination with bortezomib and daratumumab.

100 mg selinexor (on days 1, 8, 15 and 22), plus 40 mg dexamethasone (20 mg IV the day of daratumumab and selinexor and 20 mg oral administration the day after daratumumab and selinexor) both weekly as continuous therapy.

Bortezomib will be given via subcutaneous at dose of 1.3 mg/m2 once weekly on days 1, 8, 15 and 22 during the cycles 1 to cycle 8, and on day 1 and day 15 of each cycle thereafter as continuous therapy.

Daratumumab will be given via intravenous at dose of 16 mg/Kg on days 1, 8, 15 and 22 (weekly) during the cycles 1 and 2, every two weeks (on days 1 and 15) during the cycles 3 to 6 and on day 1 of each cycle thereafter as continuous therapy.

Patients may continue indefinitely and there is no maximum treatment duration

Detailed Description

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This is a Phase 2, single-arm, open, non-randomized, multicenter study of the SINE™ compound selinexor plus low-dose dexamethasone, in combination with bortezomib and daratumumab.

Sixty-two patients with R/R MM who meet eligibility criteria and have none of the exclusion criteria will be enrolled to receive SVDd until either disease progression or intolerance has occurred.

Enrolled patients will take a fixed milligram dose of 100 mg selinexor (on days 1, 8, 15 and 22), plus 40 mg dexamethasone (20 mg IV the day of daratumumab and selinexor and 20 mg oral administration the day after daratumumab and selinexor) both weekly as continuous therapy.

Bortezomib will be given via subcutaneous at dose of 1.3 mg/m2 once weekly on days 1, 8, 15 and 22 during the cycles 1 to cycle 8, and on day 1 and day 15 of each cycle thereafter as continuous therapy.

Daratumumab will be given via intravenous at dose of 16 mg/Kg on days 1, 8, 15 and 22 (weekly) during the cycles 1 and 2, every two weeks (on days 1 and 15) during the cycles 3 to 6 and on day 1 of each cycle thereafter as continuous therapy.

Patients may continue indefinitely and there is no maximum treatment duration

Conditions

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Refractory Multiple Myeloma

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

This is an investigator-sponsored, open-label, non-randomized Phase 2 study to evaluate the efficacy and safety of this combination for a total of 62 patients with refractory or relapsed/refractory MM patients. The treatment will be given until progression of the disease or inacceptable toxicity. This trial will be conducted in approximately 15-centers in Spain
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Selinexor, Daratumumab, Bortezomib and dexamethasone

Selinexor will be administered via oral at flat dose of 100 mg weekly in 4 out of each 4-week cycle plus dexamethasone 40 or 20 mg mg orally with each dose of selinexor in combination with daratumumab at dose of 16 mg/Kg iv weekly on days 1, 8, 15 and 22 during the first two cycles; on days 1 and 15 (Q2W) during the cycles 3 to 6; and on day 1 (Q4W) thereafter and bortezomib will be given via subcutaneous at dose of 1.3 mg/m2 on days 1, 8, 15 and 22 starting from the first cycle and on days 1 and 15 (Q2W) since cycle 9. Each cycle is of 4 weeks of duration

Group Type EXPERIMENTAL

Selinexor

Intervention Type DRUG

Selinexor will be administered via oral at flat dose of 100 mg weekly in 4 out of each 4-week cycle

Daratumumab

Intervention Type DRUG

daratumumab at dose of 16 mg/Kg iv weekly on days 1, 8, 15 and 22 during the first two cycles; on days 1 and 15 (Q2W) during the cycles 3 to 6; and on day 1 (Q4W) thereafter

Bortezomib

Intervention Type DRUG

bortezomib will be given via subcutaneous at dose of 1.3 mg/m2 on days 1, 8, 15 and 22 starting from the first cycle and on days 1 and 15 (Q2W) since cycle 9

Dexamethasone

Intervention Type DRUG

dexamethasone is 20mg (IV) when given on days that daratumumab is administered (as pre-infusion medication) plus 20 mg of dexamethasone (VO) the day after and the dose of dexamethasone is 40mg (VO) on days when daratumumab is not administered

Interventions

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Selinexor

Selinexor will be administered via oral at flat dose of 100 mg weekly in 4 out of each 4-week cycle

Intervention Type DRUG

Daratumumab

daratumumab at dose of 16 mg/Kg iv weekly on days 1, 8, 15 and 22 during the first two cycles; on days 1 and 15 (Q2W) during the cycles 3 to 6; and on day 1 (Q4W) thereafter

Intervention Type DRUG

Bortezomib

bortezomib will be given via subcutaneous at dose of 1.3 mg/m2 on days 1, 8, 15 and 22 starting from the first cycle and on days 1 and 15 (Q2W) since cycle 9

Intervention Type DRUG

Dexamethasone

dexamethasone is 20mg (IV) when given on days that daratumumab is administered (as pre-infusion medication) plus 20 mg of dexamethasone (VO) the day after and the dose of dexamethasone is 40mg (VO) on days when daratumumab is not administered

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patient is, in the investigator's opinion, willing and able to comply with the protocol requirements.
* Patient has given voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to their future medical care.
* Patient must be at least 18 years of age.
* Patient must have a confirmed diagnosis of symptomatic multiple myeloma and measurable secretory disease, defined as either serum monoclonal protein ≥ 0,5 g/dL or urine monoclonal (light chain) protein ≥ 200 mg/24 hours. For patients in whom measurable disease is performed by serum FLC, the involved FLC should be ≥ 10 mg/dL, with an abnormal serum FLC ratio.
* Patients must have an ECOG performance status of 0, 1 or 2.
* All patients must have received prior treatment with proteasome inhibitors and immunomodulators: A minimum of 2 consecutive cycles of proteasome inhibitors and immunomodulators are required.
* Patients must have received ≥ 3 prior lines of therapy and be refractory to the last line of therapy, or be double refractory to proteasome inhibitors and immunomodulatory drugs on their most recent therapy, regardless of the prior number lines of therapy; or patients were thought to be refractory if they had progressed on or within 60 days of treatment with bortezomib and/or lenalidomide.
* Patient has the following laboratory values within 14 days before Baseline visit (Day 1 of Cycle 1, before study drug administration): Platelet count ≥ 75 x109/L, hemoglobin ≥ 8.0g/dl and absolute neutrophil count (ANC) ≥ 1.5 x 109/L; lower values may be accepted if clearly are due to bone marrow involvement by multiple myeloma (ANC ≥ 1.0 x 109/L and platelets ≥ 50 x109/L if bone marrow infiltration \> 60%). Patients receiving hematopoietic growth factor support, including erythropoietin (EPO), darbepoetin, granulocyte-colony stimulating factor (G-CSF) may continue to do so.
* Corrected serum calcium \< 14mg/dl.
* Aspartate transaminase (AST): ≤ 2.5 x the upper limit of normal, alanine transaminase (ALT): ≤ 2.5 x the upper limit of normal, and total bilirrubin: ≤ 2.0 x the upper limit of normal.
* Calculated creatinine clearance ≥ 20 ml per minute, calculated using the formula of Cockroft and Gault:Multiply times 0.85 if the patient is female, or CrCl \>20 mL/min as measured by 24-hour urine collection
* Women of childbearing potential must be practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies: eg, established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods: condom with spermicidal foam/gel/film/cream/suppository; male partner steritilization (the vasectomized partner should be the sole partner for that subject); true abstinence (when this is in line with the preferred and usual lifestyle of the subject) during and after the study (6 months after the last dose of any component of the treatment regimen).
* A woman of childbearing potential must have a negative serum pregnancy test at screening within 10-14 days and 24 hours before commencing treatment. Females of reproductive potential must commit either to abstain continuously from heterosexual sexual intercourse or to use two methods or reliable birth control simultaneously

Exclusion Criteria

* Subject has received selinexor or daratumumab therapies previously.
* Patients who are refractory to daratumumab or CD38 targeting antibody.
* Subject has a diagnosis of plasma cell leukemia, primary amyloidosis, monoclonal gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM).
* Subject has previously received autologous stem cell transplantation within 12 weeks before Cycle Day 1, or has received other anti-myeloma treatment within 2 weeks before Cycle 1 Day 1 (with the exception of an emergency use of a short course \[maximum 4 days\] of corticosteroids \[40 mg/day dexamethasone or equivalent\]).
* Subject who had previously received allogeneic stem cell transplantation within the last year or even latter if they have evidence of graft versus host disease.
* Subject has peripheral neuropathy or neuropathic pain grade 2 or higher, as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.
* Subject has had any prior or concurrent invasive malignancy (other than myeloma) within 5 years of study start except adequately treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, localized prostate adenocarcinoma diagnosed ≥ 3 years and without evidence of biochemical failure, or other cancer for which the subject has undergone potentially curative therapy and has no evidence of that disease for ≥ 5 years.
* Subject has had radiation therapy within 28 days of Cycle 1 Day 1.
* Subject has meningeal involvement of multiple myeloma.
* Subject has known severe chronic obstructive pulmonary disease (COPD) (defined as a forced expiratory volume \[FEV\] in 1 second \<60% of predicted normal), persistent asthma, or a history of severe asthma within 5 years. Subjects with known or suspected COPD or asthma must have a FEV test during screening.
* Subjects have known moderate or severe persistent asthma within the past 2 years (see Appendix 8: National Heart, Lung, and Blood Institute (NHLBI) table of asthma severity), or currently has uncontrolled asthma of any classification. (Note that subjects who currently have controlled intermittent asthma or controlled mild ersistene asthma are allowed in the study).
* Unstable cardiovascular function:Symptomatic ischemia, or Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with 1st degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) will not be excluded), or Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or Myocardial infarction (MI) within 3 months.
* Patients with uncontrolled hypertension.
* Uncontrolled active infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose.
* Subject is known to be seropositive for history of human immunodeficiency virus (HIV) or hepatitis B (defined by a positive test for hepatitis B surface antigen \[HBsAg\] or antibodies to hepatitis B surface and core antigens \[anti HBs and anti-HBc, respectively\]) or hepatitis C (anti-HCV antibody positive or HCV-RNA quantitation positive).
* Patients with any GI dysfunction who are unable to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment
* Serious psychiatric or medical conditions that, in the opinion of the investigator, could interfere with treatment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PETHEMA Foundation

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hospital Germans Trials i Pujol

Badalona, , Spain

Site Status RECRUITING

Hospital Clinic de Barcelona

Barcelona, , Spain

Site Status RECRUITING

Hospital ICO de Girona

Girona, , Spain

Site Status RECRUITING

Hospital ICO de L'hospitalet

L'Hospitalet de Llobregat, , Spain

Site Status RECRUITING

Hospital 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Clinico de Madrid

Madrid, , Spain

Site Status RECRUITING

Hospital Morales Meseguer

Murcia, , Spain

Site Status RECRUITING

Hospital Central de Asturias

Oviedo, , Spain

Site Status RECRUITING

Clinica Universitaria de Navarra

Pamplona, , Spain

Site Status RECRUITING

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Site Status RECRUITING

Hospital Universitario de Donostia

San Sebastián, , Spain

Site Status RECRUITING

Hospital Universitario de Canarias

Santa Cruz de Tenerife, , Spain

Site Status RECRUITING

Hospital Universitario de Santiago

Santiago de Compostela, , Spain

Site Status RECRUITING

Hospital Virgen del Rocio

Seville, , Spain

Site Status RECRUITING

Hospital Dr Peset

Valencia, , Spain

Site Status RECRUITING

Countries

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Spain

Central Contacts

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Jesús San Miguel, Prof

Role: CONTACT

+34 948 255 400

Mª Victoria Mateos, Dr

Role: CONTACT

+ 34 923 291384

Facility Contacts

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Albert Oriol, Dr

Role: primary

Joan Bladé, Dr

Role: primary

Yolanda Gonzalez, Dr

Role: primary

Anna Sureda, Dr

Role: primary

Juan José Lahuerta, Dr

Role: primary

Rafael Martinez, Dr

Role: primary

Felipe de Arriba, Dr

Role: primary

Ana Pilar Gonzalez, Dr

Role: primary

Jesús San Miguel, Prof

Role: primary

Mª Victoria Mateos, Dr

Role: primary

Maialen Sirvent, Dr

Role: primary

Miguel Hernandez, Dr

Role: primary

Marta Sonia Gonzalez, Dr

Role: primary

Jesus Martín, Dr

Role: primary

Javier de la Rubia, Dr

Role: primary

Other Identifiers

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GEM- SELIBORDARA

Identifier Type: -

Identifier Source: org_study_id

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