Status:
RECRUITING
Selinexor Plus VRd in High Risk Newly Diagnosed Multiple Myeloma
Lead Sponsor:
Xia Zhongjun
Collaborating Sponsors:
Antengene Corporation
Conditions:
Multiple Myeloma
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This is a single-arm and open-label study to explore XVRd (ATG-010, Bortezomib, Lenalidomide and Dexamethasone) regimen in high-risk newly diagnosed multiple myeloma.The primary objective of the dose ...
Detailed Description
This is a single-arm and open-label study to explore XVRd (ATG-010, Bortezomib, Lenalidomide and Dexamethasone) regimen in high-risk newly diagnosed multiple myeloma. Approximately 3-42 patients will ...
Eligibility Criteria
Inclusion
- Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:
- Willing and able to written informed consent (ICF) .
- Age ≥ 18 years.
- Newly diagnosed multiple myeloma as defined by IMWG(Rajkumar, Dimopoulos et al. 2014) , measurable disease as defined IMWG 2016 criteria(Table 5) (Kumar, Paiva et al.2016), and meet at least one of the following criteria:
- Serum M-protein (SPEP) ≥ 5 g/L, If the MM type is IgA/IgD, that can be substituted by IgA/IgD quantitative level.
- 24 hours-Urinary M-protein excretion ≥ 0.2 g (200 mg)
- Serum FLC ≥ 100 mg/L with abnormal FLC ratio ( FLC Normal ratio:0.26 to 1.65)
- According to mSMART 3.0 definition for high risk multiple myeloma:
- High Risk genetic Abnormalities t(4;14) , t(14;16) , t(14;20) , Del 17p, p53 mutation, Gain 1q
- R-ISS Stage 3
- High Plasma Cell S-phase
- GEP: High risk signature
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2. ECOG PS 3 allowed, if caused by myeloma.
- Patients must have received no prior chemotherapy for multiple myeloma. Patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis). Patients must have received no prior steroid treatment for myeloma with the exception of a maximum of 14 days of treatment for symptom control.
- Adequate hepatic function: total bilirubin \< 1.5× upper limit of normal (ULN) (for patients with Gilbert's syndrome, a total bilirubin of \< 3× ULN is required), AST \< 2× ULN, and ALT \< 2× ULN.
- Adequate renal function: estimated creatinine clearance ≥ 30 mL/min (calculated using the formula of Cockroft-Gault).
- Adequate hematopoietic function within 7 days prior to C1D1 and met the following criteria: White blood cell (WBC) count ≥1.5×109/L, Absolute neutrophil count (ANC)≥1.0×109/L, Hemoglobin (HB) ≥85g/L and Platelet count (PLT) ≥75×109/L (patients whom \<50% of bone marrow nucleated cells are plasma cells) or PLT ≥ 50×109/L (patients whom ≥ 50% of bone marrow nucleated cells are plasma cells).
- Patients could not receive hematopoietic growth factor treatment within 2 weeks prior to screening, These growth factors include Erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), Granulocyte macrophages-colony stimulating factor (GM-CSF), Platelet agonist, etc (Eltrombopag, Thrombopoietin (TPO), Interleukin-11).
- Patients receive transfusions of blood products:
- At least 2 weeks elapsed between the screening hemoglobin assessment and the last red blood cell infusion,
- And at least 1 week elapsed between the screening platelet assessment and the last platelet infusion.
- Patients must be able to take prophylactic anticoagulant therapy as recommended by the study.
- Female patients of childbearing potential must meet below two criteria:
- must agree to use effective contraception methods since signature in ICF, throughout the study and for 3 months following the last dose of study treatment.
- must have a negative serum pregnancy test at screening. Note: A woman is considered of childbearing potential following menarche and until becoming postmenopausal (defined as no menstrual period for a minimum of 12 months) or permanently sterile (having undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy). A woman who is taking oral contraceptive or using intrauterine device is considered of childbearing potential.
- Male patients (including those who have received vasectomy) must use a condom if sexually active with a female of child-bearing potential throughout the study and for 3 months following the last dose of study treatment.
Exclusion
- Patients who meet any of the following criteria will not be enrolled:
- Plasma cell leukemia.
- Documented active amyloidosis.
- Involvement of the central nervous system(CNS) by Multiple myeloma.
- Prior exposure to a SINE compound, including ATG-010.
- Currently, whether or not the patient is on medication, \> Grade 2 peripheral neuropathy or ≥ Grade ≥ 2 painful neuropathy at baseline.
- Known intolerance, hypersensitivity, or contraindication to glucocorticoids, bortezomib, lenalidomide, and Selinexor (ATG-010) .
- 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 6 months prior to C1D1.
- Known positive serology for HIV or HIV seropositivity.
- Known active hepatitis A, B, or C infection; eg. positive for HCV RNA or HBV-DNA.
- Women who are pregnant or nursing.
- Life expectancy of less than 6 months.
- 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.
- 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.
- Contraindication to any of the required concomitant drugs or supportive treatments.
- Has any concurrent diseases or complications that is likely to interfere with the study procedures.
- Patients unwilling or unable to comply with the protocol.
Key Trial Info
Start Date :
July 25 2022
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 31 2025
Estimated Enrollment :
42 Patients enrolled
Trial Details
Trial ID
NCT05422027
Start Date
July 25 2022
End Date
December 31 2025
Last Update
June 17 2024
Active Locations (4)
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1
Guangdong Provincial Peoples Hospital
Guangzhou, Guangdong, China, 510000
2
Sun Yat-sen University Cancer Center; State Key Laboratory of Oncology in South China,
Guangzhou, Guangdong, China, 510060
3
Sun Yat-sen Memorial Hospital, Sun Yat-sen University
Guangzhou, Guangdong, China, 510120
4
Nanfang Hospital
Guangzhou, Guangdong, China, 510515