Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies

NCT03465540 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: 20170173
• Study Type: interventional
• Target: 24
• Locations: 6 countries
• Sites: 21

Brief Summary

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

Conditions

Multiple Myeloma; Acute Myeloid Leukemia; Non-Hodgkins Lymphoma; Myelodysplastic Syndrome; AML; MDS; NHL

Keywords

Multiple Myeloma; Acute Myeloid Leukemia; Myelodysplastic Syndrome; AML; MDS; MM; Myeloid Cell Leukemia 1 Inhibitor; MCL1 Inhibitor; MCL1

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)

  DLTs were defined as specific adverse events (AEs) that occurred in a participant during the DLT evaluation period (Day 1 to Day 28), that the investigator assessed as related to AMG 397. The grading and severity of AEs were based on the guidelines provided in the common terminology criteria for adverse events (CTCAE) version 4.03.

  28 days

• Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

  A TEAE was defined as any AE starting on or after the first dose of investigational product. Any clinically significant changes in vital signs, physical examinations, electrocardiogram (ECGs) and clinical laboratory test results were recorded as AEs. The grading and severity of adverse events were based on the guidelines provided in the CTCAE version 4.03. Treatment-related TEAEs were any events that the investigator assessed as related to AMG 397.

  Up to 30 days after last dose (Maximum time on treatment was 18 weeks for part 1a and 13 weeks for part 1b)

Secondary Outcomes (12)

• Overall Response Rate (ORR) for Participants With Multiple Myeloma (MM)

  Up to end of study (a maximum of 48 weeks)

• Overall Response Rate (ORR) for Participants With Non-Hodgkin's Lymphoma (NHL)

  Up to end of study (a maximum of 48 weeks)

• Overall Response Rate (ORR) for Participants With Acute Myeloid Leukemia (AML)

  Up to end of study (a maximum of 48 weeks)

• Progression-free Survival (PFS)

  Up to end of study (a maximum of 48 weeks)

• Overall Survival (OS)

  Up to end of study (a maximum of 48 weeks)

Study Arms (8)

Part 1A: AMG 397 Dose Escalation

EXPERIMENTAL

This arm includes subjects with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL).

Drug: AMG 397

Part 1B: AMG 397 Dose Escalation

EXPERIMENTAL

This arm includes subjects with acute myeloid leukemia (AML).

Drug: AMG 397

Part 2A: AMG 397 Monotherapy

EXPERIMENTAL

This arm includes subjects with AML or myelodysplastic syndrome (MDS).

Drug: AMG 397

Part 2B: AMG 397 Monotherapy

EXPERIMENTAL

This arm includes subjects with AML in Japan only.

Drug: AMG 397

Part 2C: AMG 397 Monotherapy

EXPERIMENTAL

This arm includes subjects with MM.

Drug: AMG 397

Part 3A: AMG 397 + Azacitidine Combotherapy

EXPERIMENTAL

This arm includes subjects MDS.

Drug: AMG 397; Drug: Azacitidine

Part 3B: AMG 397+ Azacitidine Combotherapy

EXPERIMENTAL

This arm includes subjects AML.

Drug: AMG 397; Drug: Azacitidine

Part 3C: AMG 397+ Dexamethasone Combotherapy

EXPERIMENTAL

This arm includes subjects MM.

Drug: AMG 397; Drug: Dexamethasone

Interventions

AMG 397 DRUG

AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.

Part 1A: AMG 397 Dose Escalation; Part 1B: AMG 397 Dose Escalation; Part 2A: AMG 397 Monotherapy; Part 2B: AMG 397 Monotherapy; Part 2C: AMG 397 Monotherapy; Part 3A: AMG 397 + Azacitidine Combotherapy; Part 3B: AMG 397+ Azacitidine Combotherapy; Part 3C: AMG 397+ Dexamethasone Combotherapy

Dexamethasone DRUG

Dexamethasone will be administered intravenously (IV) or orally on Days 1, 8, 15, and 22 of each 28-day cycle.

Part 3C: AMG 397+ Dexamethasone Combotherapy

Azacitidine DRUG

Azacitidine will be administered intravenously (IV) or subcutaneously (SC) daily for the first 7 days of a 28-day cycle.

Part 3A: AMG 397 + Azacitidine Combotherapy; Part 3B: AMG 397+ Azacitidine Combotherapy

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 multiple myeloma (MM), myelodysplastic syndrome (MDS), or acute myeloid leukemia (AML) and is intolerant to, or considered ineligible for available therapies known to provide clinical benefit
• MM subjects only: Measurable disease per the International Myeloma Working Group (IMWG) response criteria (assessed within 21 days prior to enrollment), as indicated by one or more of the following: cytogenic risk factor: 1q21 amplification/gain, 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
• MM subjects only: Hematological function, as follows without transfusion or growth factor support within 2 weeks prior to study day 1: absolute neutrophil count ≥ 1.0 X 109/L, hemoglobin \> 8 g/dL and platelet count ≥ 75 X 109/L
• AML subjects only: Pathologically confirmed diagnosis of AML as defined by the World Health Organisation (WHO) Classification, more than 5% blasts in bone marrow and persisting or recurring following one or more treatment courses
• MDS subjects only: pathologically confirmed diagnosis of MDS as defined by the WHO Classification, intermediate and high risk MDS and intolerant or refractory to HMA treatment
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2
• Life expectancy of \> 3 months, based on the opinion of the investigator
• 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 (TBL) \< 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 echocardiogram or multigated acquisition (MUGA) scan

You may not qualify if:

• Disease Related
• 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 before enrollment
• Candidates for stem cell transplant should have failed or are not considered eligible for either allogeneic and autologous transplant
• Other Medical Conditions
• History of other malignancy except:
• Malignancy treated with curative intent and with no known active disease present for ≥ 2 years before enrollment and felt to be at low risk for recurrence by the treating physician
• Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
• Adequately treated cervical carcinoma in situ without evidence of disease
• Adequately treated breast ductal carcinoma in situ without evidence of disease
• Prostatic intraepithelial neoplasia without evidence of prostate cancer
• Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ
• Myocardial infarction within 6 months before enrollment
• 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 before enrollment

Sponsors & Collaborators

• Amgen: lead

Study Sites (21)

University of Alabama at Birmingham

Birmingham, Alabama, 35249, United States

Location

Mayo Clinic Arizona

Phoenix, Arizona, 85054, United States

Location

Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

Location

University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Froedtert and Med College Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Institut Paoli Calmettes

Marseille, 13272, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Alexandra Hospital

Athens, 11528, Greece

Location

Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII

Bergamo, 24127, Italy

Location

Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola Malpighi

Bologna, 40138, Italy

Location

Ogaki Municipal Hospital

Ogaki-shi, Gifu, 503-8502, Japan

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Multiple Myeloma; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes

Interventions

Dexamethasone; Azacitidine

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Leukemia; Lymphoma; Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2018
• First Posted: March 14, 2018
• Study Start: August 17, 2018
• Primary Completion: July 25, 2019
• Study Completion: July 25, 2019
• Last Updated: April 12, 2023
• Results First Posted: April 12, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

JP (1); US (12); GR (1); FR (2); AU (3); IT (2)