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Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Multiple Myeloma, NHL, and AML

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: NCT03465540
Recruitment Status : Recruiting
First Posted : March 14, 2018
Last Update Posted : June 14, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:
Evaluate the safety and tolerability of AMG 397. Estimate the maximum tolerated doses (MTDs) and/or biologically active doses.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Non-Hodgkin's Lymphoma Acute Myeloid Leukemia AML NHL DLBCL Drug: AMG 397 Phase 1

Detailed Description:
This is a first-in-human (FIH), multicenter, non-randomized, open-label, phase 1 study evaluating AMG 397 administered orally once daily for 2 consecutive days followed by 5 days break at a weekly interval, as part of a 28-day treatment cycle in adult subjects with multiple myeloma, non-Hodgkin's lymphoma, and acute myeloid leukemia.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies
Actual Study Start Date : August 17, 2018
Estimated Primary Completion Date : February 17, 2021
Estimated Study Completion Date : September 29, 2022


Arm Intervention/treatment
Experimental: AMG 397 Treatment
AMG 397 administered orally once daily for 2 consecutive days followed by 5 days break at a weekly interval, as part of a 28-day treatment cycle in adult subjects with selected RR hematological malignancies
Drug: AMG 397
potent and selective inhibitor of protein-protein interactions between myeloid cell leukemia sequence 1 and pro-apoptotic members of the lymphoma/leukemia 2 family




Primary Outcome Measures :
  1. Subject incidence of dose limiting toxicity [ Time Frame: Up to 3 years ]
    Number of dose limiting toxicity

  2. Incidence of treatment-emergent adverse events, treatment-related adverse events [ Time Frame: Up to 3 years ]
    Number of adverse events

  3. Incidence of Clinically-significant changes in vital signs [ Time Frame: Up to 3 years ]
    Number of changes in vital signs

  4. Incidence of Clinically significant changes in ECGs [ Time Frame: Up to 3 years ]
    Number of changes in ECGs

  5. Incidence of clinically-significant changes in physical examinations [ Time Frame: Up to 3 years ]
    Number of changes in physical examinations

  6. Incidence of Clinically significant changes in clinical laboratory tests [ Time Frame: Up to 3 years ]
    Number of changes in clinical laboratory tests


Secondary Outcome Measures :
  1. Objective response rate (ORR) [ Time Frame: Up to 3 years ]
    Objective response rate (ORR)

  2. Duration of response [ Time Frame: Up to 3 years ]
    Duration of response

  3. Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
    Progression-free survival (PFS)

  4. Overall survival (OS) [ Time Frame: Up to 3 years ]
    Overall survival (OS)

  5. AMG 397 PK parameter of maximum observed concentration [ Time Frame: Up to 3 years ]
    AMG 397 PK parameter of maximum observed concentration

  6. PK parameter of time of maximum observed concentration (tmax) [ Time Frame: Up to 3 years ]
    PK parameter of time of maximum observed concentration (tmax)

  7. PK parameter of area under the concentration time curve (AUC) [ Time Frame: Up to 3 years ]
    PK parameter of area under the concentration time curve (AUC)

  8. PK parameter of clearance (CL) [ Time Frame: Up to 3 years ]
    PK parameter of clearance (CL)

  9. PK parameter of half-life (t1/2) [ Time Frame: Up to 3 years ]
    PK parameter of half-life (t1/2)



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:

  • Subject has provided informed consent prior to initiation of any study-specific activities/procedures
  • Age ≥ 18 years old
  • Pathologically-documented, definitively-diagnosed relapsed or refractory MM, NHL, or AML and is intolerant to, or considered ineligible for available therapies known to provide clinical benefit. -

MM subjects only: Measurable disease per the IMWG response criteria, as indicated by one or more of the following: Serum M-protein ≥ 0.5 g/dL, Urine M-protein ≥ 200 mg/24 hours. For Subjects who do not meet 1 of the 2 prior criteria: Serum Free Light Chain (sFLC) ≥ 10 mg/dL (≥ 100 mg/L) and an abnormal sFLC ratio (< 0.26 or > 1.65) as per the IMWG response criteria

  • NHL subjects only: Radiographically measurable disease with a clearly demarcated nodal lesion at least 1.5 cm in its largest dimension or a target extranodal lesion at least 1.0 cm in its largest dimension
  • AML subjects only: Pathologically confirmed diagnosis of AML as defined by the WHO Classification, More than 5% blasts in bone marrow
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
  • Able to swallow and retain orally administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption
  • Hepatic function, as follows: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN), Total bilirubin (TBIL) < 1.5 X ULN (except subjects with Gilbert's syndrome)
  • Cardiac function, as follows: Cardiac ejection fraction ≥ 50% and no evidence of pericardial effusion as determined by an ECHO or MUGA, No clinically significant ECG findings.
  • Renal function as follows: Calculated or measured creatinine clearance (CrCl) of ≥ 30 mL/minute calculated using the formula of Cockcroft and Gault [(140 - Age) × Mass (kg) / (72 × serum creatinine mg/dL)]. Multiply result by 0.85 if female.

Exclusion Criteria:

  • Previously received an allogeneic stem cell transplant within 6 months of study day 1 OR having signs or symptoms of acute or chronic graft-versus-host disease
  • Autologous stem cell transplant < 90 days prior to study day 1
  • Candidates for stem cell transplant should have failed or are not considered eligible for either allogeneic and autologous transplant
  • Myocardial infarction within 6 months of study day 1
  • Symptomatic congestive heart failure (New York Heart Association > Class II)
  • History of arterial thrombosis (eg, stroke or transient ischemic attack) in the past 6 months prior to study day 1
  • Infection requiring intravenous anti-infective treatments within 1 week of study day 1
  • Known positive results for human immunodeficiency virus (HIV)
  • Active hepatitis B and C based on the following results: Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic, hepatitis B or recent acute hepatitis B), Negative HBsAg and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B. Positive Hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C
  • Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 grade 1, or to levels dictated in the eligibility criteria with the exception of grade 2peripheral neuropathy, alopecia or toxicities from prior anti-tumor therapy that are considered irreversible (defined as having been present and stable for > 4 weeks prior to study day 1 may be allowed if they are not otherwise described in the exclusion criteria AND there is agreement to allow by both the investigator and sponsor)
  • Antitumor therapy (chemotherapy, antibody therapy, molecular-targeted therapy, retinoid therapy, or investigational agent or procedures) within 14 days of day 1
  • Prior systemic radiation therapy must have been completed at least 28 days before study day 1. Prior focal radiotherapy completed at 14 days before study day 1
  • Males and females of reproductive potential who are unwilling to practice an acceptable method(s) of effective birth control while on study through 3 months after receiving the last dose of study drug. Acceptable methods of effective birth control include sexual abstinence (males, females); vasectomy; bilateral tubal ligation/occlusion; or a condom with spermicide (men) in combination with barrier methods (diaphragm, cervical cap, or cervical sponge), hormonal birth control or IUD (females)
  • Females who are lactating/breastfeeding or who plan to breastfeed while on study through 3 months after receiving the last dose of study drug
  • Females with a positive pregnancy test or planning to become pregnant while on study through 3 months after receiving the last dose of study drug
  • Males who are unwilling to abstain from sperm donation while on study through 3 months after receiving the last dose of study drug

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): NCT03465540


Contacts
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Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

Locations
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United States, Alabama
Research Site Recruiting
Birmingham, Alabama, United States, 35294
United States, Kansas
Research Site Recruiting
Westwood, Kansas, United States, 66205
United States, Maryland
Research Site Recruiting
Baltimore, Maryland, United States, 21201
United States, Missouri
Research Site Recruiting
Saint Louis, Missouri, United States, 63110
United States, New York
Research Site Recruiting
Buffalo, New York, United States, 14263
Research Site Recruiting
New York, New York, United States, 10065
United States, Texas
Research Site Recruiting
Houston, Texas, United States, 77030
United States, Wisconsin
Research Site Recruiting
Milwaukee, Wisconsin, United States, 53226
Australia, New South Wales
Research Site Recruiting
Camperdown, New South Wales, Australia, 2050
Australia, Queensland
Research Site Recruiting
Woolloongabba, Queensland, Australia, 4102
Australia, Victoria
Research Site Recruiting
Melbourne, Victoria, Australia, 3004
France
Research Site Recruiting
Marseille Cedex 09, France, 13272
Greece
Research Site Recruiting
Athens, Greece, 11528
Italy
Research Site Recruiting
Bologna, Italy, 40138
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT03465540     History of Changes
Other Study ID Numbers: 20170173
First Posted: March 14, 2018    Key Record Dates
Last Update Posted: June 14, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
URL: https://www.amgen.com/datasharing

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

Keywords provided by Amgen:
Multiple Myeloma
Non-Hodgkin's Lymphoma
Acute Myeloid Leukemia
AML
NHL
MM
DLBCL
Myeloid Cell Leukemia 1 Inhibitor
MCL1 Inhibitor
MCL1

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Multiple Myeloma
Neoplasms, Plasma Cell
Leukemia, Myeloid, Acute
Lymphoma, Non-Hodgkin
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
Lymphoma
Lymphatic Diseases