Relapsed/Refractory AMLPhase 1NCT02520427
A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies
A Phase 1 study testing AMG 330 in people with Relapsed/Refractory AML and Minimal Residual Disease Positive AML, run by Amgen at 11 sites in 4 countries.
Trial summary
The purpose of this First-in-Human Phase 1 study is to determine if AMG 330 given as a continuous IV infusion is safe and tolerable in adult subjects that have myeloid malignancies, and to determine the maximum tolerated dose and/or a biologically active dose. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Relapsed/Refractory AML, Minimal Residual Disease Positive AML, Myelodysplastic Syndrome
- What is being tested?
- AMG 330
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 95 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 31 Aug 2015to 9 Jan 2022
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent provided
- 18 years or older
- Relapsed/refractory AML: AML as defined by the WHO Classification persisting or recurring following one or more treatment courses except promyelocytic leukemia (APML)
Who cannot join
- Active extramedullary AML in testes or central nervous system (CNS)
- Known hypersensitivity to immunoglobulins or to any other component of the IP formulation (eg, sucrose, captisol, potassium, polysorbate 80, citrate, lysine)
- Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for > 1 years before screening
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States5 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294-3300
Research Site
Duarte, California, 91010
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Seattle Cancer Care Alliance
Seattle, Washington, 98109
Wake Forest University Health Sciences
Winston-Salem, North Carolina, 27157
Germany3 sites
Universitätsklinikum Schleswig-Holstein
Kiel, 24105
Klinikum der Universität München Campus Grosshadern
München, 81377
Universitatsklinikum Ulm
Ulm, 89081
Netherlands2 sites
Research Site
Amsterdam, 1007 MB
Erasmus Medisch Centrum
Rotterdam, 3015 CE
About this study
Official title: A Phase 1 First-in-human Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 330 Administered as Continuous Intravenous Infusion in Subjects With Myeloid Malignancies
The purpose of this First-in-Human Phase 1 study is to determine if AMG 330 given as a continuous IV infusion is safe and tolerable in adult subjects that have myeloid malignancies, and to determine the maximum tolerated dose and/or a biologically active dose. The study will be conducted in multiple sites and test increasing doses of AMG 330. The safety of subjects will be monitored by intensive assessment of vital signs, electrocardiograms, physical examinations, and laboratory tests.
- Being tested
- AMG 330
- Keywords
- Amgen, Phase 1, Clinical Trial, Oncology/Hematology, Relapsed/Refractory AML, Immunotherapy
- Medical subject headings
- Leukemia, Myeloid, Acute, Myelodysplastic Syndromes, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 330Drug
0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) | Experimental | Not described Receives: Drug: AMG 330 |
| Group 2: Minimal Residual Disease Positive (MRD+) AML | Experimental | Not described Receives: Drug: AMG 330 |
| Group 3: Myelodysplastic syndrome (MDS) | Experimental | Not described Receives: Drug: AMG 330 |
| Group 4: R/R AML with alternative pretreatment | Experimental | Not described Receives: Drug: AMG 330 |
| Group 5: R/R AML with alternative dose schedule | Experimental | Not described Receives: Drug: AMG 330 |
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)
A participant was not DLT-evaluable if they dropped out before completion of the DLT window (14 days) for reasons other than an adverse event related to study drug or the participant had not received investigational product (IP) treatment for at least 14 days at the target dose for a 3- or 4-week cycle or at least 7 days at a target dose for a 2- week cycle. Furthermore, following drug interruptions, if a participant was unable to complete 2 repeat cycles for reasons other than DLT, the participant was not DLT evaluable.
Measured: Day 1 to Day 14
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
The severity of TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. The general guideline for assessment ranged from Grade 1 to 5, with higher grades indicating a worse outcome, and included: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death.
Measured: Day 1 until 30 days after last dose. Median duration of treatment was: Group 1 - 29.0 days; Group 2 - 29.0 days; Group 3 - 49.50 days; Group 4 - 23.50 days
Secondary outcomes (16)
Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation
Number of participants with a binding anti-body positive result at any timepoint post-baseline who had a negative or no result at baseline.
Measured: Baseline until the end of study, up to approximately 6 months
Response Rate in Participants With R/R AML
Response for participants with R/R AML was defined as the percentage of participants with complete response (CR)/complete remission with incomplete count recovery (CRi)/morphologic leukemia-free state (MLFS) [per modified international working group (IWG) criteria] or complete remission with partial hematologic recovery (CRh).
Measured: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Response Rate in Participants With MRD-positive AML
Response for participants with MRD-positive AML was defined as the percentage of participants with a conversion from MRD+ status with 0.1% threshold to CRMDR- or CRiMD-.
Measured: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Response Rate in Participants With MDS
Response for participants with MDS was defined as the percentage of participants with CR or marrow complete remission per IWG.
Measured: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Duration of Response
Duration of response was defined as the interval from the date of the first disease assessment indicating an overall response to the first documented relapse, disease progression, or death due to any cause, whichever occurs first.
Measured: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Time to Response
Time to response was defined as the interval from the first administration of AMG 330 to the first documentation of response.
Measured: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Event-free Survival
Event-free survival was defined as the interval from first administration of AMG 330 to the earliest of date of treatment failure, relapse for responders, or death due to any cause.
Measured: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Overall Survival
Overall survival was defined as the time from enrollment until death due to any cause.
Measured: Baseline until the end of study, up to approximately 6 months
14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 330
Measured: 14 day infusion duration: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: t1/2 z of AMG 330
Measured: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)
14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 330
Measured: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: Css After End of Infusion of AMG 330
Measured: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)
14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 330
Measured: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: Vz of AMG 330
Measured: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 day)
14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 330
Measured: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: CL of AMG 330
Measured: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2015 (estimated)
- Study start31 Aug 2015
- Primary completion9 Jan 2022
- Study completion9 Jan 2022
Why it stopped: Amgen strategic business decision to cancel following portfolio review, re-prioritization.
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 Relapsed/Refractory AMLStudies 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
- 95 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
- NCT02520427
- Sponsor's protocol ID
- 20120252
- Other IDs
- 2014-004462-20, 2014
- Status last verified
- Feb 2024
- First submitted
- 17 Jun 2015
- Last updated
- 31 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- 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 31 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 First-in-human Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 330 Administered as Continuous Intravenous Infusion in Subjects With Myeloid Malignancies
- ClinicalTrials.gov ID
- NCT02520427
- Acronym / sponsor ID
- 20120252
- Keywords
- Amgen, Phase 1, Clinical Trial, Oncology/Hematology, Relapsed/Refractory AML, Immunotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Amgen strategic business decision to cancel following portfolio review, re-prioritization.
- Enrolment
- 95 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 31 Aug 2015 (actual)
- Primary completion
- 9 Jan 2022 (actual)
- Study completion
- 9 Jan 2022 (actual)
- First posted
- 11 Aug 2015 (estimated)
- Results
- Posted 31 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this First-in-Human Phase 1 study is to determine if AMG 330 given as a continuous IV infusion is safe and tolerable in adult subjects that have myeloid malignancies, and to determine the maximum tolerated dose and/or a biologically active dose. The study will be conducted in multiple sites and test increasing doses of AMG 330. The safety of subjects will be monitored by intensive assessment of vital signs, electrocardiograms, physical examinations, and laboratory tests.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Group 1: Relapsed/Refractory Acute Myeloid Leukemia (R/R AML) | Experimental | Drug: AMG 330 |
| Group 2: Minimal Residual Disease Positive (MRD+) AML | Experimental | Drug: AMG 330 |
| Group 3: Myelodysplastic syndrome (MDS) | Experimental | Drug: AMG 330 |
| Group 4: R/R AML with alternative pretreatment | Experimental | Drug: AMG 330 |
| Group 5: R/R AML with alternative dose schedule | Experimental | Drug: AMG 330 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Informed consent provided
- 18 years or older
- Relapsed/refractory AML: AML as defined by the WHO Classification persisting or recurring following one or more treatment courses except promyelocytic leukemia (APML)
Key exclusion criteria (3 listed)
- Active extramedullary AML in testes or central nervous system (CNS)
- Known hypersensitivity to immunoglobulins or to any other component of the IP formulation (eg, sucrose, captisol, potassium, polysorbate 80, citrate, lysine)
- Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for > 1 years before screening
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 3300.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days. | Drug | Group 1: Relapsed/Refractory Acute Myeloid Leukemia (R/R AML), Group 2: Minimal Residual Disease Positive (MRD+) AML, Group 3: Myelodysplastic syndrome (MDS), Group 4: R/R AML with alternative pretreatment, Group 5: R/R AML with alternative dose schedule |
Primary outcome
Number of Participants Who Experienced a Dose-limiting Toxicity (DLT)
Time frame: Day 1 to Day 14
A participant was not DLT-evaluable if they dropped out before completion of the DLT window (14 days) for reasons other than an adverse event related to study drug or the participant had not received investigational product (IP) treatment for at least 14 days at the target dose for a 3- or 4-week cycle or at least 7 days at a target dose for a 2- week cycle. Furthermore, following drug interruptions, if a participant was unable to complete 2 repeat cycles for reasons other than DLT, the participant was not DLT evaluable.
Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
Time frame: Day 1 until 30 days after last dose. Median duration of treatment was: Group 1 - 29.0 days; Group 2 - 29.0 days; Group 3 - 49.50 days; Group 4 - 23.50 days
The severity of TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. The general guideline for assessment ranged from Grade 1 to 5, with higher grades indicating a worse outcome, and included: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death.
16 secondary outcomes
Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation
Time frame: Baseline until the end of study, up to approximately 6 months
Response Rate in Participants With R/R AML
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Response Rate in Participants With MRD-positive AML
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Response Rate in Participants With MDS
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Duration of Response
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Time to Response
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Event-free Survival
Time frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months
Overall Survival
Time frame: Baseline until the end of study, up to approximately 6 months
14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 330
Time frame: 14 day infusion duration: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: t1/2 z of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)
14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: Css After End of Infusion of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)
14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: Vz of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 day)
14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)
28 Day Infusion Duration: CL of AMG 330
Time frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2024.
- 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
11 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 330 in people with Relapsed/Refractory AML and Minimal Residual Disease Positive AML, run by Amgen at 11 sites in 4 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 3 inclusion and 3 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 31 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Germany, Netherlands, Canada. 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 31 Jul 2024). 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: Day 1 to Day 14). 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 31 Jul 2024.