Clinical trial NCT04877275: ATG-010(Selinexor) in Combination With Chemotherapy in RRMM
Official title: Selinexor in Combination With Chemotherapy to Treat Relapsed/Refractory Multiple Myeloma Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Multiple Myeloma
Keywords: Selinexor
ATG-010
Multiple Myeloma
Relapsed/Refractory Multiple Myeloma
Lead sponsor: Wuhan Union Hospital, China
Sponsor class: OTHER
First posted: 2021-05-07
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a single-arm that includes two experimental arms,Selinexor(ATG-010) in Combination with Chemotherapy to Treat Relapsed/Refractory Multiple Myeloma Patients.To evaluate efficacy and safety of ATG-010 in combination with chemotherapy in RRMM patients received at least one prior lines of therapy

Detailed description: This is a single-arm and open-label phase II study of Relapsed/Refractory Multiple Myeloma patients who have received at least one prior lines of treatment therapy; This study includes two experimental arms. Arm I is given XDd regimen (ATG-010 80mg/d QW, Pegylated liposomal doxorubicin 25mg/m2, d1and Dexamethasone 40mg/d QW) in approximately 25 subjects. Arm II is given XCd regimen (ATG-010 100mg/d QW, Cyclophosphamide 300mg/m2, d1and Dexamethasone 40mg/d QW). Both arms are 4 weeks per cycle and include a total of 12 cycles.

Eligibility criteria: Inclusion Criteria:

Patients must meet all of the following inclusion criteria to be eligible to enroll in this study:

1. Known and written informed consent (ICF) voluntarily.
2. Age ≥ 18 years and ≤ 75 years.
3. Patients with multiple myeloma who have received first-line treatment (induction, autologous transplantation and maintenance as the same first-line treatment) and achieved at least partial remission in induction.
4. At or after accepting first-line regimen, subjects must have progression disease (PD) recorded which is determined by researcher according to IMWG criteria.
5. Any clinically significant non-hematological toxicities (except for hair loss, peripheral neuropathy, which is otherwise stipulated in Article 13 of the exclusion criteria) that relevant to previous therapies must have resolved to ≤Grade 2 prior to first dose of study drug.
6. Left ventricular ejection fraction（LVEF ）≥50% by an echocardiogram or MUGA scan in 42 days before the first administration
7. Adequate hepatic function: total bilirubin \< 2× upper limit of normal (ULN) (for patients with Gilbert's syndrome, a total bilirubin of \< 3× ULN is required), AST \< 2.5× ULN, and ALT \< 2.5× ULN.
8. Adequate renal function: estimated creatinine clearance ≥ 20 mL/min (calculated using the formula of Cockroft-Gault).
9. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
10. Measurable MM as defined by at least one of the following:

    1. Serum M-protein (SPEP) ≥ 5 g/L
    2. 24 hours-Urinary M-protein excretion ≥ 0.2 g (200 mg)
    3. Serum FLC ≥ 100 mg/L with abnormal FLC ratio
11. Expected survival is more than 6 months.
12. Adequate hematopoietic function (no platelet transfusion within 2 weeks prior to screening test):

    1. Hemoglobin level ≥ 60 g/L
    2. ANC ≥ 1,000/mm3 (1.0×109/L)
    3. Platelet count ≥ 75,000/mm3 (75×109/L)
13. Female patients of childbearing potential must meet below two criteria:

    1. 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.
    2. 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.
14. 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 Criteria:

Patients who meet any of the following criteria will not be enrolled:

1. Asymptomatic (smoldering) MM.
2. Plasma cell leukemia.
3. Documented active amyloidosis.
4. Previously refractory or intolerant to combined drugs.
5. Pregnancy or breastfeeding.
6. Major surgery was performed within 4 weeks prior to the first study.
7. Patients with active, unstable cardiovascular diseases, fits any of the following:

   1. Symptomatic ischemia, or
   2. Uncontrolled clinically-significant conduction abnormalities (e.g., patients with ventricular tachycardia on antiarrhythmics are excluded; patients with first-degree atrioventricular (AV) block or asymptomatic left anterior fascicular block/right bundle branch block (LAFB/RBBB) are allowed), or
   3. Congestive heart failure (CHF) of New York Heart Association (NYHA) ≥ Grade 3, or
   4. Acute myocardial infarction (AMI) within 3 months prior to the first dose of study drug.
8. Uncontrolled active infection within 1 week prior to the first dose of study drug.
9. Known HIV positive.
10. Known active hepatitis A, B, or C infection; or known positive for HCV RNA or HBsAg.

    (Note: patients with HBsAg negative but HBc Ab positive need further HBV-DNA test, excluded if HBV-DNA ≥103 , if HBV-DNA \<103 need anti-viral drugs)
11. Prior malignancy that required treatment or has shown evidence of recurrence (except for skin basal-cell carcinoma and in-situ carcinoma including squamous cell carcinoma, bladder cancer in situ, endometrial cancer in situ, cervical cancer in situ/atypical hyperplasia, prostate cancer incidental finding (T1a or T1b), or breast cancer in situ) within 5 years prior to the first dose of study drug.
12. Active GI dysfunction interfering with the ability to swallow tablets, or any GI dysfunction that could interfere with absorption of study treatment.
13. Grade ≥ 3 peripheral neuropathy, and Grade ≥ 2 painful neuropathy, within 3 weeks prior to the first dose of study drug.
14. Serious, active psychiatric, or medical conditions which, in the opinion of the Investigator, could interfere with study treatment.
15. Participation in an investigational anti-cancer clinical study within 3 weeks or 5 half-lives (T1/2) prior to the first dose of study drug.
16. Received ASCT within 12 weeks prior to the first dose of study drug or previous allogeneic stem cell transplantation (no time limitation).
17. Treatment with an approved or trial anticancer drug was given within 3 weeks or 5 half-lives (T1/2) （With a short time priority） prior to the first study.
18. Prior exposure to a SINE compound.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: Assessed from the date of first dose of study treatment until the date that PD assessed up to 12months
Secondary outcomes:
measure: Minimal Residual Disease (MRD)
timeFrame: 12 months
measure: Overall Survival (OS)
timeFrame: 12 months
measure: Progression-Free Survival (PFS)
timeFrame: 12 months
measure: Duration of Response (DOR)
timeFrame: 12 months
measure: Clinical Benefit Rate (CBR)
timeFrame: 12 months
measure: Disease Control Rate (DCR)
timeFrame: 12 months
measure: Number of Participants with Adverse Events
timeFrame: From first dose of study drug administration to end of treatment (up to 12 months)
Other outcomes:
Locations:
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Wuhan
country: China
facility: Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Xi'an
country: China
facility: The First Affiliated Hospital of Air Force Medical University
state: Shanxi
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
Study officials:
affiliation: Wuhan Union Hospital, China
name: Chunyan Sun, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: