Multiple MyelomaPhase 1NCT03465540
Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 397 in Subjects With Selected Relapsed or Refractory Hematological Malignancies
A Phase 1 study testing AMG 397, Dexamethasone and Azacitidine in people with Multiple Myeloma and Acute Myeloid Leukemia, run by Amgen at 21 sites in 6 countries.
Trial summary
Evaluate the safety and tolerability of AMG 397. Estimate the maximum tolerated doses (MTDs) and/or biologically active doses. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Myeloma, Acute Myeloid Leukemia, Non-Hodgkins Lymphoma
- What is being tested?
- AMG 397, Dexamethasone and Azacitidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 21 sitesin 6 countries
- Study dates
- 17 Aug 2018to 25 Jul 2019
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 18Show fewer
- 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
- no ECG findings representing a recent cardiac injury within 6 months before enrollment
- 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
Who cannot join
- 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:
Show all 46Show fewer
- 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
- Uncontrollable active infection requiring intravenous anti-infective treatments within 1 week before enrollment
- 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
- Females of reproductive potential who are unwilling to practice acceptable methods of highly effective contraception while on study through 8 months after receiving the last dose of study drug. Males who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use a condom with or without spermicide while on study through 5 months after receiving the last dose of study drug if sexually active with a female of childbearing potential
- Females who are lactating/breastfeeding or who plan to breastfeed while on study through 8 months after receiving the last dose of study drug
- Females with a positive pregnancy test or planning to become pregnant while on study through 8 months after receiving the last dose of study drug
- Males who are unwilling to abstain from sperm donation while on study through 8 months after receiving the last dose of study drug
- History or evidence of any other clinically significant disorder, condition or disease that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to subject safety or interfere with the study evaluation, procedures or completion
- Use of any over-the-counter or prescription medications within 14 days or 5 half-lives (whichever is longer), prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor
- Use of herbal medicines (eg, St. John's wort), vitamins, and supplements consumed by the subject within 14 days prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor
- Use of any known inhibitors of P-gp within 14 days or 5 half-lives (whichever is longer) or grapefruit juice or grapefruit containing products within 7 days prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor
- Use of known CYP3A4 sensitive substrates, (with a narrow therapeutic window), within 14 days or 5 half-lives (whichever is longer) of the drug or its major active metabolite, whichever is longer, prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor
- Use of known P-gp substrates (with a narrow therapeutic window) within 14 days or 5 half-lives (whichever is longer) prior to study day 1 that was not reviewed and approved by the principal investigator and the Amgen medical monitor
- Subject likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures (eg, long term follow-up) to the best of the subject and investigator's knowledge
- Known sensitivity to any of the products or component to be administered during dosing
- MM subjects with any of the following criteria are excluded:
- Multiple myeloma with IgM subtype
- POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes)
- Existing plasma cell leukemia
- Waldenstrom's macroglobulinemia
- Amyloidosis
- AML subjects with the following criteria are excluded:
- Circulating white blood cells > 25,000/μl. Hydroxyurea to control peripheral blood leukemic cell counts, within 24 hours of study day 1 is permitted
- Promyelocytic leukemia
- AML/MDS subjects fit for intensive salvage therapy
- Subjects with elevated cardiac troponin above the manufacturer's 99th percentile upper reference limit for ADVIA Centaur XP assay at screening performed by the central laboratory (Covance)
- Subjects with evidence of recent cardiac injury at screening based on creatine kinase-muscle/brain (CK-MB), N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP), and ECG assessments at screening
- Subjects with MDS that are eligible for hematopoietic stem cell transplant (HSCT)
Trial locations and contacts
21 sites in 6 countries.
21 sites in 6 countries
United States12 sites
University of Maryland Greenebaum Cancer Center
Baltimore, Maryland, 21201
University of Alabama at Birmingham
Birmingham, Alabama, 35249
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Roswell Park Cancer Institute
Buffalo, New York, 14263
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Mayo Clinic Florida
Jacksonville, Florida, 32224
Froedtert and Med College Wisconsin
Milwaukee, Wisconsin, 53226
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Mayo Clinic Arizona
Phoenix, Arizona, 85054
Mayo Clinic Rochester
Rochester, Minnesota, 55905
Washington University
St Louis, Missouri, 63110
University of Kansas Cancer Center
Westwood, Kansas, 66205
Australia3 sites
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050
The Alfred Hospital
Melbourne, Victoria, 3004
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102
France2 sites
Institut Paoli Calmettes
Marseille, 13272
Institut Gustave Roussy
Villejuif, 94805
Italy2 sites
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
Bergamo, 24127
Azienda Ospedaliera Universitaria di Bologna Policlinico S Orsola Malpighi
Bologna, 40138
About this study
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
Evaluate the safety and tolerability of AMG 397. Estimate the maximum tolerated doses (MTDs) and/or biologically active doses.
Read the detailed description
This is a first-in-human (FIH), multicenter, non-randomized, open-label, phase 1 study evaluating AMG 397 administered orally once weekly, as part of a 28-day treatment cycle in adult subjects with selected relapsed or refractory hematological malignancies
- Conditions
- Multiple Myeloma, Acute Myeloid Leukemia, Non-Hodgkins Lymphoma, Myelodysplastic Syndrome, AML, MDS
- Being tested
- AMG 397, Dexamethasone, Azacitidine
- Keywords
- Multiple Myeloma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, AML, MDS, MM, Myeloid Cell Leukemia 1 Inhibitor, MCL1 Inhibitor, MCL1
- Medical subject headings
- Multiple Myeloma, Leukemia, Myeloid, Acute, Lymphoma, Non-Hodgkin, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 397Drug
AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle.
DexamethasoneDrug
Dexamethasone will be administered intravenously (IV) or orally on Days 1, 8, 15, and 22 of each 28-day cycle.
AzacitidineDrug
Azacitidine will be administered intravenously (IV) or subcutaneously (SC) daily for the first 7 days of a 28-day cycle.
| Study group | Role | What they receive |
|---|---|---|
| Part 1A: AMG 397 Dose Escalation | Experimental | This arm includes subjects with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL). Receives: Drug: AMG 397 |
| Part 1B: AMG 397 Dose Escalation | Experimental | This arm includes subjects with acute myeloid leukemia (AML). Receives: Drug: AMG 397 |
| Part 2A: AMG 397 Monotherapy | Experimental | This arm includes subjects with AML or myelodysplastic syndrome (MDS). Receives: Drug: AMG 397 |
| Part 2B: AMG 397 Monotherapy | Experimental | This arm includes subjects with AML in Japan only. Receives: Drug: AMG 397 |
| Part 2C: AMG 397 Monotherapy | Experimental | This arm includes subjects with MM. Receives: Drug: AMG 397 |
| Part 3A: AMG 397 + Azacitidine Combotherapy | Experimental | This arm includes subjects MDS. Receives: Drug: AMG 397; Drug: Azacitidine |
| Part 3B: AMG 397+ Azacitidine Combotherapy | Experimental | This arm includes subjects AML. Receives: Drug: AMG 397; Drug: Azacitidine |
| Part 3C: AMG 397+ Dexamethasone Combotherapy | Experimental | This arm includes subjects MM. Receives: Drug: AMG 397; Drug: Dexamethasone |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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)
ORR was assessed for participants with MM using response criteria per International Myeloma Working Group (IMWG).
ORR was defined as the percentage of participants who experienced either one of the following based on investigator assessment:
- partial response (PR)
- very good partial response (VGPR)
- complete response (CR)
- stringent complete response (sCR)
Measured: Up to end of study (a maximum of 48 weeks)
Overall Response Rate (ORR) for Participants With Non-Hodgkin's Lymphoma (NHL)
ORR was assessed for participants with NHL using response criteria per Lugano Classification.
ORR was defined as the percentage of participants who experienced either of the following based on investigator assessment:
- partial metabolic response/ PR
- complete metabolic response/ CR
Measured: Up to end of study (a maximum of 48 weeks)
Overall Response Rate (ORR) for Participants With Acute Myeloid Leukemia (AML)
ORR was assessed for participants with AML using response criteria per European Leukemia Network Response Criteria.
ORR was defined as the percentage of participants who experienced either of the following based on investigator assessment:
- PR
- morphological leukemia-free state (MLFS)
- complete remission with incomplete hematologic recovery (CRi)
- complete remission
- complete remission without minimal residual disease (CRmrd-).
Measured: Up to end of study (a maximum of 48 weeks)
Progression-free Survival (PFS)
PFS was calculated as time from first dose of investigational product date to disease progression date or death due to any cause, whichever was earlier.
PFS time in months: (date of disease progression or death - first dose date +1)/30.4.
Measured: Up to end of study (a maximum of 48 weeks)
Overall Survival (OS)
OS was defined as the time from first dose of investigational product date until death due to any cause.
OS time in months: (date of death - first dose date +1)/30.4.
Measured: Up to end of study (a maximum of 48 weeks)
Time to Response (TTR)
TTR was defined as the time from the first dose of investigational product until the first documentation of objective response. Only participants who achieved an objective response were evaluated for TTR.
TTR time in months: (date of the first observation of response - first dose of IP date +1)/30.4.
Measured: Up to end of study (a maximum of 48 weeks)
Duration of Response (DOR)
DOR was only planned to be calculated for participants who achieved response (PR or better). DOR was defined as time from the first observation indicating a response to the subsequent date of disease progression or death, whichever was earlier.
DOR time in months: (date of disease progression or death - date of the first observation of response +1)/30.4.
Measured: Up to end of study (a maximum of 48 weeks)
Maximum Observed Concentration (Cmax) of AMG 397
Predose data for Day 2 were analyzed/included with the Day 1 data.
Measured: Cycle 1 (cycle = 28 days): Predose, 1, 2, 3, 5, 8 & 12 hours postdose on Day 1; predose, 1, 2, 3, 5, 8, 12, 24 & 48 hours postdose on Day 2
Time to Maximum Observed Concentration (Tmax) for AMG 397
Predose data for Day 2 were analyzed/included with the Day 1 data.
Measured: Cycle 1 (cycle = 28 days): Predose, 1, 2, 3, 5, 8 & 12 hours postdose on Day 1; predose, 1, 2, 3, 5, 8, 12, 24 & 48 hours postdose on Day 2
Area Under the Concentration Time Curve From Time 0 to 168 Hours (AUC0-168) for AMG 397
Measured: Cycle 1 (cycle = 28 days): Predose, 3, 5, & 8 hours postdose on days 1 (12 hours postdose on Day 1 only), 8 & 15, predose & 8 hours postdose on Day 22 & days 2, 3, 4, 9, 16, 17, 18 & 23; Cycles 2, 3 & 4 (cycle = 28 days): Predose on days 2, 8, 15 & 22
Clearance (CL) of AMG 397
Measured: Cycle 1 (cycle = 28 days): Predose, 3, 5, & 8 hours postdose on days 1 (12 hours postdose on Day 1 only), 8 & 15, predose & 8 hours postdose on Day 22 & days 2, 3, 4, 9, 16, 17, 18 & 23; Cycles 2, 3 & 4 (cycle = 28 days): Predose on days 2, 8, 15 & 22
Half-life (t1/2) of AMG 397
Measured: Cycle 1 (cycle = 28 days): Predose, 3, 5, & 8 hours postdose on days 1 (12 hours postdose on Day 1 only), 8 & 15, predose & 8 hours postdose on Day 22 & days 2, 3, 4, 9, 16, 17, 18 & 23; Cycles 2, 3 & 4 (cycle = 28 days): Predose on days 2, 8, 15 & 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start17 Aug 2018
- Primary completion25 Jul 2019
- Study completion25 Jul 2019
Why it stopped: Strategic decisions
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Multiple MyelomaStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03465540
- Sponsor's protocol ID
- 20170173
- Status last verified
- Apr 2023
- First submitted
- 8 Mar 2018
- Last updated
- 12 Apr 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03465540
- Acronym / sponsor ID
- 20170173
- Conditions
- Multiple Myeloma, Acute Myeloid Leukemia, Non-Hodgkins Lymphoma, Myelodysplastic Syndrome, AML, MDS
- Keywords
- Multiple Myeloma, Acute Myeloid Leukemia, Myelodysplastic Syndrome, AML, MDS, MM, Myeloid Cell Leukemia 1 Inhibitor, MCL1 Inhibitor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Strategic decisions
- Enrolment
- 24 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 17 Aug 2018 (actual)
- Primary completion
- 25 Jul 2019 (actual)
- Study completion
- 25 Jul 2019 (actual)
- First posted
- 14 Mar 2018 (actual)
- Results
- Posted 12 Apr 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Evaluate the safety and tolerability of AMG 397. Estimate the maximum tolerated doses (MTDs) and/or biologically active doses.
Detailed description
This is a first-in-human (FIH), multicenter, non-randomized, open-label, phase 1 study evaluating AMG 397 administered orally once weekly, as part of a 28-day treatment cycle in adult subjects with selected relapsed or refractory hematological malignancies
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Part 1A: AMG 397 Dose Escalation | Experimental | Drug: AMG 397This arm includes subjects with multiple myeloma (MM) or non-Hodgkin's lymphoma (NHL). |
| Part 1B: AMG 397 Dose Escalation | Experimental | Drug: AMG 397This arm includes subjects with acute myeloid leukemia (AML). |
| Part 2A: AMG 397 Monotherapy | Experimental | Drug: AMG 397This arm includes subjects with AML or myelodysplastic syndrome (MDS). |
| Part 2B: AMG 397 Monotherapy | Experimental | Drug: AMG 397This arm includes subjects with AML in Japan only. |
| Part 2C: AMG 397 Monotherapy | Experimental | Drug: AMG 397This arm includes subjects with MM. |
| Part 3A: AMG 397 + Azacitidine Combotherapy | Experimental | Drug: AMG 397, Drug: AzacitidineThis arm includes subjects MDS. |
| Part 3B: AMG 397+ Azacitidine Combotherapy | Experimental | Drug: AMG 397, Drug: AzacitidineThis arm includes subjects AML. |
| Part 3C: AMG 397+ Dexamethasone Combotherapy | Experimental | Drug: AMG 397, Drug: DexamethasoneThis arm includes subjects MM. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- 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
Key exclusion criteria (46 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 397AMG 397 will be administered orally once or twice weekly as part of a 28-day treatment cycle. | Drug | 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 |
| DexamethasoneDexamethasone will be administered intravenously (IV) or orally on Days 1, 8, 15, and 22 of each 28-day cycle. | Drug | Part 3C: AMG 397+ Dexamethasone Combotherapy |
| AzacitidineAzacitidine will be administered intravenously (IV) or subcutaneously (SC) daily for the first 7 days of a 28-day cycle. | Drug | Part 3A: AMG 397 + Azacitidine Combotherapy, Part 3B: AMG 397+ Azacitidine Combotherapy |
Primary outcome
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Time frame: 28 days
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.
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Time frame: Up to 30 days after last dose (Maximum time on treatment was 18 weeks for part 1a and 13 weeks for part 1b)
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.
12 secondary outcomes
Overall Response Rate (ORR) for Participants With Multiple Myeloma (MM)
Time frame: Up to end of study (a maximum of 48 weeks)
Overall Response Rate (ORR) for Participants With Non-Hodgkin's Lymphoma (NHL)
Time frame: Up to end of study (a maximum of 48 weeks)
Overall Response Rate (ORR) for Participants With Acute Myeloid Leukemia (AML)
Time frame: Up to end of study (a maximum of 48 weeks)
Progression-free Survival (PFS)
Time frame: Up to end of study (a maximum of 48 weeks)
Overall Survival (OS)
Time frame: Up to end of study (a maximum of 48 weeks)
Time to Response (TTR)
Time frame: Up to end of study (a maximum of 48 weeks)
Duration of Response (DOR)
Time frame: Up to end of study (a maximum of 48 weeks)
Maximum Observed Concentration (Cmax) of AMG 397
Time frame: Cycle 1 (cycle = 28 days): Predose, 1, 2, 3, 5, 8 & 12 hours postdose on Day 1; predose, 1, 2, 3, 5, 8, 12, 24 & 48 hours postdose on Day 2
Time to Maximum Observed Concentration (Tmax) for AMG 397
Time frame: Cycle 1 (cycle = 28 days): Predose, 1, 2, 3, 5, 8 & 12 hours postdose on Day 1; predose, 1, 2, 3, 5, 8, 12, 24 & 48 hours postdose on Day 2
Area Under the Concentration Time Curve From Time 0 to 168 Hours (AUC0-168) for AMG 397
Time frame: Cycle 1 (cycle = 28 days): Predose, 3, 5, & 8 hours postdose on days 1 (12 hours postdose on Day 1 only), 8 & 15, predose & 8 hours postdose on Day 22 & days 2, 3, 4, 9, 16, 17, 18 & 23; Cycles 2, 3 & 4 (cycle = 28 days): Predose on days 2, 8, 15 & 22
Clearance (CL) of AMG 397
Time frame: Cycle 1 (cycle = 28 days): Predose, 3, 5, & 8 hours postdose on days 1 (12 hours postdose on Day 1 only), 8 & 15, predose & 8 hours postdose on Day 22 & days 2, 3, 4, 9, 16, 17, 18 & 23; Cycles 2, 3 & 4 (cycle = 28 days): Predose on days 2, 8, 15 & 22
Half-life (t1/2) of AMG 397
Time frame: Cycle 1 (cycle = 28 days): Predose, 3, 5, & 8 hours postdose on days 1 (12 hours postdose on Day 1 only), 8 & 15, predose & 8 hours postdose on Day 22 & days 2, 3, 4, 9, 16, 17, 18 & 23; Cycles 2, 3 & 4 (cycle = 28 days): Predose on days 2, 8, 15 & 22
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
21 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 397, Dexamethasone and Azacitidine in people with Multiple Myeloma and Acute Myeloid Leukemia, run by Amgen at 21 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 46 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 12 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in United States, Australia, France, Italy, Greece and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 12 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2023.