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出境医 / 临床实验 / A Study of Evaluating the Safety and Efficacy of ATG-010 in Relapsed Refractory Multiple Myeloma (MARCH)

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

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
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated 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
Estimated Primary Completion Date : June 1, 2021
Estimated Study Completion Date : December 1, 2021
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
Layout table for eligibility information
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

Contacts
Layout table for location contacts
Contact: Shimin Sun, MD 13701803117 jasmine.sun@antengene.com
Contact: Zhigang Lv, MD zhigang.lv@antengene.com

Locations
Show Show 17 study locations
Sponsors and Collaborators
Antengene Corporation
Investigators
Layout table for investigator information
Study Director: Ying Jiao, MD Medical Monitor
Tracking Information
First Submitted Date  ICMJE April 30, 2019
First Posted Date  ICMJE May 9, 2019
Last Update Posted Date December 24, 2020
Actual Study Start Date  ICMJE September 2, 2019
Estimated Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 7, 2019) 		Overall Response Rate (ORR) [ Time Frame: 12 months ]
To determine the overall response rate according to IMWG 2016 criteria
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 7, 2019)
  • Survival Rate (SR) [ Time Frame: 12 months ]
    To evaluate survival rate at 6 months, 9 months, 12 months
  • Time To Progression (TTP) [ Time Frame: 12 months ]
    To evaluate duration from initiation of treatment to disease progression
  • Progression-Free Survival (PFS) [ Time Frame: 12 months ]
    To evaluate progression-free survival
  • Duration of Response (DOR) [ Time Frame: 12 months ]
    To evaluate duration of response
  • Clinical Benefit Rate (CBR) [ Time Frame: 12 months ]
    Clinical Benefit Rate (CBR=ORR+Minor Response [MR])
  • Disease Control Rate (DCR) [ Time Frame: 12 months ]
    Disease Control Rate (DCR=CBR+Stable Disease[SD])
  • Overall Survival (OS) [ Time Frame: 12 months ]
    The estimates of Kaplan-Meier
  • Minimal Residual Disease (MRD) [ Time Frame: 12 months ]
    To evaluate the minimal residual disease in CR and sCR patients
  • 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.
  • Peak Plasma Concentration (Cmax) [ Time Frame: 12 months ]
    To evaluate the maximum plasma concentration (Cmax) of ATG-010 in Chinese patient population
  • Peak Plasma Concentration（Tmax） [ Time Frame: 12 months ]
    To evaluate the time to reach Cmax of ATG-010 in Chinese patient population
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Evaluating the Safety and Efficacy of ATG-010 in Relapsed Refractory Multiple Myeloma
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Relapse/Refractory Multiple Myeloma
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: ATG-010 + Dexamethasone
Open-label ATG-010 80mg plus Dexamethasone 20 mg
Intervention: Drug: ATG-010
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 7, 2019) 		82
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2021
Estimated Primary Completion Date June 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Shimin Sun, MD 13701803117 jasmine.sun@antengene.com
Contact: Zhigang Lv, MD zhigang.lv@antengene.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03944057
Other Study ID Numbers  ICMJE ATG-010-MM-001
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Antengene Corporation
Study Sponsor  ICMJE Antengene Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Ying Jiao, MD Medical Monitor
PRS Account Antengene Corporation
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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