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SELIBORDARA: Selinexor, Bortezomib and Daratumumab in Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT03589222
Recruitment Status : Recruiting
First Posted : July 17, 2018
Last Update Posted : July 27, 2018
Sponsor:
Information provided by (Responsible Party):
PETHEMA Foundation

Tracking Information
First Submitted Date  ICMJE June 12, 2018
First Posted Date  ICMJE July 17, 2018
Last Update Posted Date July 27, 2018
Actual Study Start Date  ICMJE July 15, 2018
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 4, 2018)
Number of responses type to treatment [ Time Frame: 1 year ]
Note overall response rate (ORR), including stringent complete responses, complete responses (CR), very good partial responses (VGPR), and partial responses (PR) according to the International Myeloma Working Group Criteria (IMWG)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03589222 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 4, 2018)
Incidence of Treatment-Emergent Adverse Events [ Time Frame: 2 years ]
Note incidence of clinical and laboratory toxicities.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE SELIBORDARA: Selinexor, Bortezomib and Daratumumab in Multiple Myeloma
Official Title  ICMJE An Open-label, Multicenter, Phase 2 Trial of Selinexor (KPT-330), Bortezomib and Low-dose Dexamethasone Plus Daratumumab (SELIBORDARA) for the Treatment of Patients With Refractory or Relapsed and Refractory Multiple Myeloma
Brief Summary

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

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

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
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
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Refractory Multiple Myeloma
Intervention  ICMJE
  • Drug: Selinexor
    Selinexor will be administered via oral at flat dose of 100 mg weekly in 4 out of each 4-week cycle
  • 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
  • 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
  • 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
Study Arms  ICMJE Experimental: 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
Interventions:
  • Drug: Selinexor
  • Drug: Daratumumab
  • Drug: Bortezomib
  • Drug: Dexamethasone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 4, 2018)
62
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date June 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Jesús San Miguel, Prof +34 948 255 400 sanmiguel@unav.es
Contact: Mª Victoria Mateos, Dr + 34 923 291384 mateos@usal.es
Listed Location Countries  ICMJE Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03589222
Other Study ID Numbers  ICMJE GEM- SELIBORDARA
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party PETHEMA Foundation
Study Sponsor  ICMJE PETHEMA Foundation
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account PETHEMA Foundation
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP