Overview

SELIBORDARA: Selinexor, Bortezomib and Daratumumab in Multiple Myeloma

Status:
Recruiting
Trial end date:
2023-08-01
Target enrollment:
0
Participant gender:
All
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
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
PETHEMA Foundation
Treatments:
Antibodies, Monoclonal
BB 1101
Bortezomib
Daratumumab
Dexamethasone
Dexamethasone acetate
Criteria
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consent may be withdrawn by the patient at any time without prejudice to their future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