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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03944057
Recruitment Status : Recruiting
First Posted : May 9, 2019
Last Update Posted : October 11, 2019
Sponsor:
Information provided by (Responsible Party):
Antengene Corporation

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 82 participants
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 : December 1, 2020
Estimated Study Completion Date : April 1, 2021


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




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



Information from the National Library of Medicine

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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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03944057


Contacts
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Contact: Shimin Sun, MD 13701803117 jasmine.sun@antengene.com
Contact: Xiang Hua, MD 13701258278 eric.hua@antengene.com

Locations
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China, Tianjin
Tianjin blood research institute Recruiting
Tianjin, Tianjin, China, 300020
Contact: Lugui Qiu, MD       qiulg@ihcams.ac.cn   
Sponsors and Collaborators
Antengene Corporation
Investigators
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Study Director: Ying Jiao, MD Medical Monitor

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Responsible Party: Antengene Corporation
ClinicalTrials.gov Identifier: NCT03944057     History of Changes
Other Study ID Numbers: ATG-010-MM-001
First Posted: May 9, 2019    Key Record Dates
Last Update Posted: October 11, 2019
Last Verified: June 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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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
Dexamethasone
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors