A Study of Evaluating the Safety and Efficacy of ATG-010 in Relapsed Refractory Multiple Myeloma (MARCH)

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

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.

Study Overview

• Status: Completed
• Conditions: Relapse/Refractory Multiple Myeloma
• Intervention / Treatment: Drug: ATG-010

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.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100191
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100020
      • Beijing Chao-Yang Hospital, Capital Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital
    • Guangzhou, Guangdong, China, 510000
      • Guangdong Provincial Peoples Hospital
    • Guanzhou, Guangdong, China, 510060
      • Sun Yat-Sen University Cancer Center
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Henan Cancer Hospital
  • Hunan
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central Suoth University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210029
      • The First Affilate Hospital with Nanjing Medical University
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital Of Nanchang University
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Bethune Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200003
      • Shanghai Changzheng Hospital
    • Shanghai, Shanghai, China, 200233
      • Shanghai Sixth People's Hospital Affiliate Shanghai JiaoTong University
  • Shanxi
    • Xi'an, Shanxi, China, 710032
      • Xijing Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300020
      • Tianjin blood research institute
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • The first Affiliated Hospital, Zhejiang University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ATG-010 + Dexamethasone; Open-label ATG-010 80mg plus Dexamethasone 20 mg	Drug: ATG-010; ATG-010 (Selinexor) will be given at an oral fixed milligram (mg) dose of 80 mg twice weekly each week for four-week cycles (total of 8 ATG-010 doses per cycle). Dexamethasone 20 mg will be given with each dose of ATG-010 (Selinexor); Other Names: Selinexor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	The primary efficacy endpoint of ORR consists of proportion of patients who achieve PR, VGPR, CR, or sCR according to IMWG 2016 criteria: CR means Negative IFE of serum and urine, disappearance of any soft tissue plasmacytomas (SPD), and <5% plasma cells in bone marrow aspirates;; sCR means CR as defined above plus normal FLC ratio and absence of clonal cells in bone marrow biopsy by immunohistochemistry (κ/λ ratio ≤ 4:1 or ≥ 1:2 for κ and λ patients, respectively, after counting ≥ 100 plasma cells);; VGPR means Serum and urine M-protein detectable by IFE but not on electrophoresis, or ≥90% reduction in serum M-protein plus urine M-protein level <100 mg per 24 hours;; PR means ≥50% reduction of serum M-protein plus reduction in 24-hour urine M-protein by ≥90% or to <200 mg per 24 hours. If the serum and urine M-protein are unmeasurable, a ≥50% decrease in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	To evaluate progression-free survival	12 months

Collaborators and Investigators

• Sponsor: Antengene Corporation
• Investigators: Study Director: Ying Jiao, MD, Medical Monitor

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2019
• Primary Completion (Actual): February 25, 2022
• Study Completion (Actual): February 25, 2022

Study Registration Dates

• First Submitted: April 30, 2019
• First Submitted That Met QC Criteria: May 7, 2019
• First Posted (Actual): May 9, 2019

Study Record Updates

• Last Update Posted (Actual): June 15, 2023
• Last Update Submitted That Met QC Criteria: May 21, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: ATG-010-MM-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes