Trial Title:
Selinexor, Venetoclax, and Dexamethasone (XVenD) in t(11;14)-Positive Relapsed/Refractory Multiple Myeloma
NCT ID:
NCT05530421
Condition:
Relapsed and Refractory Multiple Myeloma
Conditions: Official terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Dexamethasone
Venetoclax
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Selinexor
Description:
Selinexor tablets will be administered orally (PO) once per day at assigned dosage and
frequency per protocol.
Arm group label:
XVenD Group
Other name:
Xpovio
Intervention type:
Drug
Intervention name:
Venetoclax
Description:
Venetoclax tablets will be administered orally (PO) once per day at assigned dosage and
frequency per protocol.
Arm group label:
XVenD Group
Other name:
Venclexta
Other name:
Venclyxto
Intervention type:
Drug
Intervention name:
Dexamethasone
Description:
Dexamethasone tablets will be administered orally (PO) once per day at assigned dosage
and frequency per protocol.
Arm group label:
XVenD Group
Other name:
Decadron
Other name:
Ozurdex
Other name:
Dexycu
Summary:
The purpose of this research is to determine whether the combination of selinexor,
venetoclax, and dexamethasone therapy can increase anti-cancer effects in patients with
translocation 11;14-positive (t(11;14)), relapsed/refractory myeloma (RRMM).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patients must have a documented diagnosis of multiple myeloma defined by the
International Myeloma Working Group Criteria (IMWG).5 Patients at initial diagnosis
must have had a serum M-protein ≥ 3 g/dL and/or bone marrow plasma cells ≥10%, and
at least one of the following:
1. Anemia: Hemoglobin ≤10 g/dL, or
2. Renal failure: serum creatinine ≥ 2.0 mg/dL, or
3. Hypercalcemia: Ca ≥10.5 mg/dL, or
4. Lytic bone lesions on X-ray, CT, or Positron emission tomography/Computed
Tomography (PET/CT), or
5. ≥ 2 focal lesions on spinal magnetic resonance imaging (MRI), or
6. ≥ 60% bone marrow plasma cells, or Involved/un-involved serum free light chain
ratio ≥ 100. Age ≥18 years of age on day of signing informed consent.
2. Patients must have had a bone marrow (BM) biopsy proven plasma cell myeloma
harboring the t(11;14) translocation as reported by a Clinical Laboratory
Improvement Amendments (CLIA) certified assay (i.e. local fluorescence in situ
hybridization (FISH) testing). BM biopsy can be performed at time of enrollment or
documented FISH results (i.e. original FISH report) can be used.
3. Must have Relapsed or Relapsed and Refractory Multiple Myeloma. Patients must have
documented evidence of having received two prior lines of therapy and be refractory
to, not a candidate for (ineligible), or intolerant of at least one immunomodulatory
(IMiD), one proteasome inhibitor, and one anti-cluster of differentiation 38
(anti-CD38) monoclonal antibody-based treatments.
4. Documented measurable disease based on the IMWG guidelines within the 4 weeks prior
to registration defined by any one of the following criteria:
1. Serum monoclonal protein ≥ 0.5 g/dl
2. Urine monoclonal protein >200 mg/24 hour
3. Serum immunoglobulin free light chain >10 mg/dL AND abnormal kappa/lambda ratio
4. Bone marrow plasma cells ≥ 30%
5. A measurable lesion on PET/CT or MRI ≥ 2 cm
5. Be ≥ 18 years of age on day of signing informed consent
6. Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of ≤ 3 (Appendix
A)
7. Adequate organ function as evidenced by the following laboratory parameters within 4
weeks of C1D1:
Hematologic:
1. Absolute neutrophil count (ANC) 1000/microliter (mcL) (granulocyte-colony
stimulating factor (G-CSF) allowed)
2. Platelets ≥ 50,000/mcL (transfusions and stimulators permitted); in patients
with >50% bone marrow plasma cells, platelets ≥ 30,000/mcL
3. Hemoglobin ≥ 8 g/dL (transfusions permitted)
Non-hematologic:
4. Serum creatinine ≤ 1.5 X ULN (except if due to myeloma) or calculated
creatinine clearance (CrCl)/Estimated glomerular filtration rate (eGFR) (by
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of
Diet in Renal Disease (MDRD), or Cockcroft-Gault) ≥ 15 mL/min/1.73 m2
5. Serum total bilirubin ≤ 1.5 X ULN or direct bilirubin ≤ ULN for patients with
total bilirubin levels > 1.5 ULN (except patients with Gilbert's syndrome who
must have a total bilirubin of < 3 X ULN)
6. Aspartate transaminase (SGOT) and alanine transaminase (SGPT) ≤ 2.5 X ULN
8. Female patients of childbearing potential 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 90 days following
the last dose of study treatment.
9. 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.
Exclusion Criteria:
1. Has received selinexor or another specific inhibitor of nuclear exporter (SINE)
compound previously.
2. Has any concurrent medical condition or disease (eg, uncontrolled active
hypertension, uncontrolled active diabetes, active systemic infection, etc.) that is
likely to interfere with study procedures.
3. 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.
4. Known intolerance, hypersensitivity, or contraindication to glucocorticoids.
5. Pregnant or breastfeeding females.
6. Active, unstable cardiovascular function, as indicated by the presence of
symptomatic ischemia, or Uncontrolled clinically significant conduction
abnormalities (eg, patients with ventricular tachycardia on anti-arrhythmics are
excluded; patients with first degree atrioventricular block or asymptomatic left
anterior fascicular block/right bundle branch block will not be excluded), or
Congestive heart failure of New York Heart Association Class ≥3 or known left
ventricular ejection fraction <40%, or Myocardial infarction within 3 months prior
to C1D1.
7. Subjects with active hepatitis B virus (Hep B) are allowed if antiviral therapy for
hepatitis B has been given for >8 weeks and viral load is <100 IU/ml prior to first
dose of trial treatment. Subjects with untreated hepatitis C virus (HCV) are
allowed. Subjects with Human Immunodeficiency Virus (HIV) who have cluster of
differentiation 4-positive (CD4+) T-cell counts ≥ 350 cells/µL and no history of
AIDS-defining opportunistic infections in the last year are allowed.
8. 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.
9. 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)
(https://www.nccn.org/guidelines/category_3) for antiemesis and anorexia/cachexia
(palliative care).
10. 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.
11. Contraindication to any of the required concomitant drugs or supportive treatments.
12. Patients unwilling or unable to comply with the protocol or known mental or physical
illness that would interfere with cooperation with the requirements of the trial or
confound the results or interpretation of the results of the trial and, in the
opinion of the treating investigator, would make the patient inappropriate for entry
into the study.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of Miami, Lennar Foundation Medical Center
Address:
City:
Coral Gables
Zip:
33146
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alanna Vossen
Phone:
305-243-7701
Email:
avossen@miami.edu
Contact backup:
Last name:
Dickran Kazandjian, MD
Phone:
718-795-6027
Email:
dkazandjian@miami.edu
Facility:
Name:
University of Miami, Sylvester Comprehensive Cancer Center at Deerfield Beach
Address:
City:
Deerfield Beach
Zip:
33442
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alanna Vossen
Phone:
305-243-7701
Email:
avossen@miami.edu
Contact backup:
Last name:
Dickran Kazandjian, MD
Phone:
718-795-6027
Email:
dkazandjian@miami.edu
Facility:
Name:
University of Miami, Sylvester Comprehensive Cancer Center
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Last name:
Alanna Vossen
Phone:
305-243-7701
Email:
avossen@miami.edu
Contact backup:
Last name:
Dickran Kazandjian, MD
Email:
dkazandjian@miami.edu
Investigator:
Last name:
Dickran Kazandjian, MD
Email:
Principal Investigator
Start date:
March 26, 2023
Completion date:
March 26, 2028
Lead sponsor:
Agency:
University of Miami
Agency class:
Other
Collaborator:
Agency:
Karyopharm Therapeutics Inc
Agency class:
Industry
Source:
University of Miami
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05530421
