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

• ClinicalTrials.gov Identifier: NCT03944057
• Recruitment Status: Completed
• First Posted: May 9, 2019
• Last Update Posted: July 28, 2022
• Sponsor: Antengene Corporation
• Information provided by (Responsible Party): Antengene Corporation

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Relapse/Refractory Multiple Myeloma	Drug: ATG-010	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 82 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: September 2, 2019
• Actual Primary Completion Date: February 25, 2022
• Actual Study Completion Date: February 25, 2022

Arms and Interventions

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 Name: Selinexor

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: 12 months ]
   To determine the overall response rate according to IMWG 2016 criteria

Secondary Outcome Measures :

1. Survival Rate (SR) [ Time Frame: 12 months ]
   To evaluate survival rate at 6 months, 9 months, 12 months
2. Time To Progression (TTP) [ Time Frame: 12 months ]
   To evaluate duration from initiation of treatment to disease progression
3. Progression-Free Survival (PFS) [ Time Frame: 12 months ]
   To evaluate progression-free survival
4. Duration of Response (DOR) [ Time Frame: 12 months ]
   To evaluate duration of response
5. Clinical Benefit Rate (CBR) [ Time Frame: 12 months ]
   Clinical Benefit Rate (CBR=ORR+Minor Response [MR])
6. Disease Control Rate (DCR) [ Time Frame: 12 months ]
   Disease Control Rate (DCR=CBR+Stable Disease[SD])
7. Overall Survival (OS) [ Time Frame: 12 months ]
   The estimates of Kaplan-Meier
8. Minimal Residual Disease (MRD) [ Time Frame: 12 months ]
   To evaluate the minimal residual disease in CR and sCR patients
9. The incidence of treatment emergent adverse events (TEAEs) & SAE assessed by CTCAE v4.03 [ Time Frame: 12 months ]
   The treatment emergent adverse events (TEAEs) & SAE case No. in total subject No.
10. Peak Plasma Concentration (Cmax) [ Time Frame: 12 months ]
    To evaluate the maximum plasma concentration (Cmax) of ATG-010 in Chinese patient population
11. Peak Plasma Concentration（Tmax） [ Time Frame: 12 months ]
    To evaluate the time to reach Cmax of ATG-010 in Chinese patient population

Eligibility Criteria

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

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/mm3
   3. Platelet count ≥ 75,000/mm3 (patients in whom < 50% of bone marrow nucleated cells are plasma cells) or ≥ 50,000/mm3 (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.

Contacts and Locations

Locations

China, Beijing

Beijing Chao-Yang Hospital, Capital Medical University

Beijing, Beijing, China, 100020

Peking University Third Hospital

Beijing, Beijing, China, 100191

China, Guangdong

Guangdong Provincial Peoples Hospital

Guangzhou, Guangdong, China, 510000

Nanfang Hospital

Guangzhou, Guangdong, China, 510515

Sun Yat-Sen University Cancer Center

Guanzhou, Guangdong, China, 510060

China, Henan

Henan Cancer Hospital

Zhengzhou, Henan, China, 450003

China, Hunan

The Third Xiangya Hospital of Central Suoth University

Changsha, Hunan, China, 410013

China, Jiangsu

The First Affilate Hospital with Nanjing Medical University

Nanjing, Jiangsu, China, 210029

The First Affiliated Hospital of Soochow University

Suzhou, Jiangsu, China, 215006

China, Jiangxi

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, China, 330006

China, Jilin

The First Bethune Hospital of Jilin University

Changchun, Jilin, China, 130021

China, Liaoning

Shengjing Hospital of China Medical University

Shenyang, Liaoning, China, 110004

China, Shanghai

Shanghai Changzheng Hospital

Shanghai, Shanghai, China, 200003

Shanghai Sixth People's Hospital Affiliate Shanghai JiaoTong University

Shanghai, Shanghai, China, 200233

China, Shanxi

Xijing Hospital

Xi'an, Shanxi, China, 710032

China, Tianjin

Tianjin blood research institute

Tianjin, Tianjin, China, 300020

China, Zhejiang

The First Affiliated Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, China, 310003

Sponsors and Collaborators

Antengene Corporation

Investigators

• Study Director: Ying Jiao, MD; Medical Monitor

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Antengene Corporation
• ClinicalTrials.gov Identifier: NCT03944057
• Other Study ID Numbers: ATG-010-MM-001
• First Posted: May 9, 2019
• Last Update Posted: July 28, 2022
• Last Verified: July 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases