Clinical trial NCT03944057: A Study of Evaluating the Safety and Efficacy of ATG-010 in Relapsed Refractory Multiple Myeloma
Official title: An Open-Label, Single-Arm Study of ATG-010 Plus Dexamethasone in Patients With Multiple Myeloma Refractory to Prior Treatment With Immunomodulatory Agents and Proteasome Inhibitor
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Relapse/Refractory Multiple Myeloma
Lead sponsor: Antengene Corporation
Sponsor class: INDUSTRY
First posted: 2019-05-09
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open-label, single-arm study of ATG-010 (selinexor) plus low-dose Dexamethasone (Sd) in patients with multiple myeloma previously treated with lenalidomide and bortezomib refractory to prior treatment with immunomodulatory agents and proteasome Inhibitors.

Detailed description: This is a single-arm, open-label, multicenter study of ATG-010 (Selinexor) plus low dose Dexamethasone dosed twice weekly each week in four-week cycles, in patients with triple-refractory MM. The population refractory for the primary efficacy analysis will contain only patients with triple-MM enrolled. PK analysis would be performed which would contain approximately 30% of the patients enrolled. Safety analyses will be performed on the overall population of patients who received at least one dose of study drug among triple-refractory patient populations. Patients will receive treatment until progressive disease (PD), death, toxicity that cannot be managed by standard care, or withdrawal, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent in accordance with federal, local, and institutional guidelines.
2. Age ≥ 18 years at the time of signing informed consent.
3. Patients must have previously received including proteasome inhibitors (PI) (i.e., lenalidomide) and immunomodulatory drugs (i.e., bortezomib) and were refractory to both drugs.
4. Any clinically significant non-hematological toxicities (except for peripheral neuropathy as described in exclusion criterion #17) that patients experienced from treatments in previous clinical studies must have resolved to Grade ≤ 2 by Cycle 1 Day 1.
5. Adequate hepatic function within 21 days prior to Cycle 1 Day 1: total bilirubin \< 2x upper limit of normal (ULN) (except patients with Gilbert's syndrome who must have a total bilirubin of \< 3x ULN), AST \< 2.5x ULN and ALT \< 2.5x ULN.
6. Adequate renal function within 21 days prior to Cycle 1 Day 1: estimated creatinine clearance of ≥ 20 mL/min, calculated using the formula of cockroft and gault.
7. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
8. Measurable MM based on IMWG guidelines.
9. Adequate hematopoietic function within 21 days prior to Cycle 1 Day 1 (See Exclusion Criterion #20 for transfusion washout periods for RBCs and platelets):

   1. Hemoglobin level ≥ 8.5 g/dL
   2. ANC ≥ 1000/mm\^3
   3. Platelet count ≥ 75,000/mm\^3 (patients in whom \< 50% of bone marrow nucleated cells are plasma cells) or ≥ 50,000/mm\^3 (patients in whom ≥ 50% of bone marrow nucleated cells are plasma cells. \[Platelet transfusions \< 1 week prior to Cycle 1 Day 1 are prohibited (see below).\]
10. Female subjects of child-bearing potential must have both of the following:

    1. Agree to the use of two study physician-approved contraceptive methods simultaneously, or practice complete abstinence starting at the time of ICF signature, while on study medication, and 3 months following the last dose of study drug.
    2. Have negative serum pregnancy test result at screening.

Exclusion Criteria:

* The presence of any of the following will exclude a subject from enrollment:

  1. Active smoldering MM.
  2. Active plasma cell leukemia.
  3. Documented systemic amyloid light chain amyloidosis.
  4. Active central nervous system (CNS) MM.
  5. Pregnancy or breastfeeding.
  6. Chemotherapy ≤ 4 week, radiation and immunotherapy ≤ 4 weeks prior to Cycle 1 Day 1, and radio-immunotherapy 6 weeks prior to Cycle 1 Day 1.
  7. Active graft vs. host disease (after allogeneic stem cell transplantation) at Cycle 1 Day 1
  8. Life expectancy of \< 4 months.
  9. Major surgery within four weeks prior to Cycle 1 Day 1.
  10. Active, unstable cardiovascular function:

      1. Symptomatic ischemia, or
      2. 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
      3. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or
      4. Myocardial infarction (MI) within 3 months prior to Cycle 1 Day 1.
  11. Prior exposure to a SINE compound, including ATG-010.

Primary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: 12 months
Secondary outcomes:
measure: Progression-Free Survival (PFS)
timeFrame: 12 months
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Chao-Yang Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University Third Hospital
state: Beijing
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital
state: Guangdong
city: Guanzhou
country: China
facility: Sun Yat-Sen University Cancer Center
state: Guangdong
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
state: Henan
city: Changsha
country: China
facility: The Third Xiangya Hospital of Central Suoth University
state: Hunan
city: Nanjing
country: China
facility: The First Affilate Hospital with Nanjing Medical University
state: Jiangsu
city: Suzhou
country: China
facility: The First Affiliated Hospital of Soochow University
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: Shengjing Hospital of China Medical University
state: Liaoning
city: Shanghai
country: China
facility: Shanghai Changzheng Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital Affiliate Shanghai JiaoTong University
state: Shanghai
city: Xi'an
country: China
facility: Xijing Hospital
state: Shanxi
city: Tianjin
country: China
facility: Tianjin blood research institute
state: Tianjin
city: Hangzhou
country: China
facility: The First Affiliated Hospital, Zhejiang University School of Medicine
state: Zhejiang
Study officials:
affiliation: Medical Monitor
name: Ying Jiao, MD
role: STUDY_DIRECTOR
References:
citation: Qiu L, Xia Z, Fu C, Chen W, Chang C, Fang B, An G, Wei Y, Cai Z, Gao S, Weng J, Chen L, Jing H, Li F, Liu Z, Chen X, Liu J, Wang A, Yu Y, Xiang W, Lynch K, Yu Z, Fu W. Selinexor plus low-dose dexamethasone in Chinese patients with relapsed/refractory multiple myeloma previously treated with an immunomodulatory agent and a proteasome inhibitor (MARCH): a phase II, single-arm study. BMC Med. 2022 Apr 5;20(1):108. doi: 10.1186/s12916-022-02305-4.