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

Sponsor
Antengene Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT03944057
Collaborator
(none)
82
Enrollment
17
Locations
1
Arm
29.8
Actual Duration (Months)
4.8
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

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
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
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 :
Sep 2, 2019
Actual Primary Completion Date :
Feb 25, 2022
Actual Study Completion Date :
Feb 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 Names:
  • Selinexor

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [12 months]

      To determine the overall response rate according to IMWG 2016 criteria

    Secondary Outcome Measures

    1. Survival Rate (SR) [12 months]

      To evaluate survival rate at 6 months, 9 months, 12 months

    2. Time To Progression (TTP) [12 months]

      To evaluate duration from initiation of treatment to disease progression

    3. Progression-Free Survival (PFS) [12 months]

      To evaluate progression-free survival

    4. Duration of Response (DOR) [12 months]

      To evaluate duration of response

    5. Clinical Benefit Rate (CBR) [12 months]

      Clinical Benefit Rate (CBR=ORR+Minor Response [MR])

    6. Disease Control Rate (DCR) [12 months]

      Disease Control Rate (DCR=CBR+Stable Disease[SD])

    7. Overall Survival (OS) [12 months]

      The estimates of Kaplan-Meier

    8. Minimal Residual Disease (MRD) [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 [12 months]

      The treatment emergent adverse events (TEAEs) & SAE case No. in total subject No.

    10. Peak Plasma Concentration (Cmax) [12 months]

      To evaluate the maximum plasma concentration (Cmax) of ATG-010 in Chinese patient population

    11. Peak Plasma Concentration（Tmax） [12 months]

      To evaluate the time to reach Cmax of ATG-010 in Chinese patient population

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    6. 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.

    7. 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.

    8. Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.

    9. Measurable MM based on IMWG guidelines.

    10. 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).]

    4. Female subjects of child-bearing potential must have both of the following:

    5. 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.

    6. 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:

    11. Symptomatic ischemia, or

    12. 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

    13. Congestive heart failure (CHF) of New York Heart Association (NYHA) Class ≥ 3, or

    14. Myocardial infarction (MI) within 3 months prior to Cycle 1 Day 1.

    15. Prior exposure to a SINE compound, including ATG-010.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Beijing Chao-Yang Hospital, Capital Medical University Beijing Beijing China 100020
    2 Peking University Third Hospital Beijing Beijing China 100191
    3 Guangdong Provincial Peoples Hospital Guangzhou Guangdong China 510000
    4 Nanfang Hospital Guangzhou Guangdong China 510515
    5 Sun Yat-Sen University Cancer Center Guanzhou Guangdong China 510060
    6 Henan Cancer Hospital Zhengzhou Henan China 450003
    7 The Third Xiangya Hospital of Central Suoth University Changsha Hunan China 410013
    8 The First Affilate Hospital with Nanjing Medical University Nanjing Jiangsu China 210029
    9 The First Affiliated Hospital of Soochow University Suzhou Jiangsu China 215006
    10 The First Affiliated Hospital of Nanchang University Nanchang Jiangxi China 330006
    11 The First Bethune Hospital of Jilin University Changchun Jilin China 130021
    12 Shengjing Hospital of China Medical University Shenyang Liaoning China 110004
    13 Shanghai Changzheng Hospital Shanghai Shanghai China 200003
    14 Shanghai Sixth People's Hospital Affiliate Shanghai JiaoTong University Shanghai Shanghai China 200233
    15 Xijing Hospital Xi'an Shanxi China 710032
    16 Tianjin blood research institute Tianjin Tianjin China 300020
    17 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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Antengene Corporation
    ClinicalTrials.gov Identifier:
    NCT03944057
    Other Study ID Numbers:
    • ATG-010-MM-001
    First Posted:
    May 9, 2019
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    Jul 1, 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

    Study Results

    No Results Posted as of Jul 28, 2022