Higher Risk Myelodysplastic SyndromePhase 1NCT05209152
AMG 176 With Azacitidine in Subjects With Myelodysplastic Syndrome /Chronic Myelomonocytic Leukemia
A Phase 1 study testing AMG 176 and Azacitidine in people with Higher Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia, run by Amgen at 1 site in United States.
Trial summary
The main objective is to assess the safety, tolerability, and efficacy of AMG 176 as monotherapy and in combination with the 7-day regimen of azacitidine for the treatment of Higher-Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia (HR-MDS/CMML). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Higher Risk Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia
- What is being tested?
- AMG 176 and Azacitidine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Nov 2022to 19 Dec 2023
- Phase
- Phase 1
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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years of age
- For Part 1, participants have R/R MDS post-HMA failure, defined as prior receipt of 4 cycles of HMA therapy (including but not limited to decitabine, azacitidine, investigational HMAs such as SGI-110, and oral HMAs such as oral decitabine and cedazuridine [ASTX727] and oral azacitidine [CC-486]) with failure to attain a response or progression of disease or relapse at any time after prior response to HMA therapy
- Note: participants with HR-CMML (CMML-1 or 2 by World Health Organization [WHO]) are eligible. Hydroxyurea administration will be allowed on the study to lower the white cell count to <= 10 000/μL prior to the initiation of therapy
- For Part 2, participants will be divided into 2 cohorts:
- HMA Failure Cohort: participants with R/R MDS post-HMA failure. Participants who have previously received venetoclax are eligible and will be stratified accordingly in the HMA failure cohort;
- Newly Diagnosed Cohort: Participants with treatment-naïve newly diagnosed HR-MDS (revised International Prognostic Scoring System [IPSS-R] score >3.5) are eligible for enrollment only after all prior cohorts have been completed. Hydroxyurea administration will be allowed on the study to lower the white cell count to <= 10 000/μL prior to the initiation of therapy. Participants with HR-CMML (CMML-1 or 2 by WHO) are eligible
Who cannot join
- Participants with newly diagnosed MDS with Revised International Prognostic Scoring System (IPSS-R) lower-risk category (IPSS-R score < 3.5)
- Participants with CMML-0 by WHO
- History of other malignancy within the past 2 years prior to enrollment (with some exceptions as listed in full list of criteria)
- Excluded prior and/or concomitant therapies as listed in the full list of criteria
- Participants who are fit and deemed eligible by the investigator for intensive salvage therapy
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
About this study
Official title: A Phase 1 Study of AMG 176 as Monotherapy and in Combination With Azacitidine in Higher-Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia
The main objective is to assess the safety, tolerability, and efficacy of AMG 176 as monotherapy and in combination with the 7-day regimen of azacitidine for the treatment of Higher-Risk Myelodysplastic Syndrome and Chronic Myelomonocytic Leukemia (HR-MDS/CMML).
Read the detailed description
This study is a Phase 1 clinical trial designed to assess the safety, tolerability, and efficacy of AMG 176 as monotherapy and in combination with the 7-day regimen of azacitidine for the treatment of HR-MDS/CMML. Participants will be treated with intravenous (IV) AMG 176 and IV or subcutaneous (SC) azacitidine.
- Being tested
- AMG 176, Azacitidine
- Keywords
- Higher Risk Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndrome, Myelomonocytic Leukemia
- Medical subject headings
- Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 176Drug
Administered as an intravenous (IV) infusion.
AzacitidineDrug
Administered as an IV infusion or subcutaneous (SC) injection.
| Study group | Role | What they receive |
|---|---|---|
| Part 1A - AMG 176 Monotherapy (Dose Exploration) | Experimental | Two dose levels of AMG 176 will be tested in Part 1A to find the optimal biological dose/minimum safe biologically effective dose (OBD/MSBED). Receives: Drug: AMG 176 |
| Part 1B - AMG 176 and Azacitidine Combination Therapy (Dose Exploration) | Experimental | After the OBD is found in Part 1A, two dose levels of AMG 176 in combination with azacitidine will be tested in Part 1B to find the OBD/MSBED. Receives: Drug: AMG 176; Drug: Azacitidine |
| Part 2 - AMG 176 and Azacitidine Combination Therapy (Dose Expansion) | Experimental | After the completion of Part 1, the Part 2 dose expansion phase will begin at the OBD/MSBED identified in Part 1.
Venetoclax-naïve and venetoclax-exposed R/R HR-MDS participants after HMA failure will be enrolled along with participants with newly diagnosed HR-MDS/CMML. Receives: Drug: AMG 176; Drug: Azacitidine |
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 graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and included the below if considered by the investigator to be related to AMG 176: Grade 3 or higher non-hematological or a Grade 4 hematologic adverse event (AE) during the DLT observation period in Part 1.
CTCAE Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 results in death.
Measured: Day 1 to day 28 of cycle 1 (each cycle was 28 days)
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An AE was defined as any untoward medical occurrence in a clinical trial participants. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to 28 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered possibly related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, and clinical laboratory tests were recorded as TEAEs. A serious TEAE resulted in death, was immediately life threatening, required or prolonged in-patient hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event.
Measured: Day 1 cycle 1 to 30 days after the last dose of AMG 176 or end of study, whichever occurred earlier (cycle length = 28 days). Median treatment duration was 2.7 months
Secondary outcomes (9)
Number of Participants With a Response According to the Uniform Response Criteria for MDS/Myeloproliferative Neoplasm (MPN)
A responder was assessed as having complete remission (CR) or partial remission (PR). Non-responders had stable disease, progressive disease or were not evaluable.
CR: ≤ 5% myeloblasts with normal maturation of all cell lines and return to normal cellularity; osteomyelofibrosis was absent or equal to mild reticulin fibrosis; resolution of extramedullary disease present before therapy.
PR: normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts reduced by 50% but >5% of cellularity except in cases of MDS/MPN with ≤ 5% blasts at baseline.
Progression: ≥ 50% reduction from maximum response levels in granulocytes or platelets, and/or reduction in hemoglobin by ≥ 1.5 g/dL in the absence of another explanation; transfusion dependence.
Measured: Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months
Time to a Response According to the Uniform Response Criteria for MDS/MPN
A responder was assessed as having CR or PR. CR: ≤ 5% myeloblasts with normal maturation of all cell lines and return to normal cellularity; osteomyelofibrosis was absent or equal to mild reticulin fibrosis; resolution of extramedullary disease present before therapy.
PR: normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts reduced by 50% but >5% of cellularity except in cases of MDS/MPN with ≤ 5% blasts at baseline.
Measured: Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months
Duration of Response According to the Uniform Response Criteria for MDS/MPN
A responder was assessed as having CR or PR. CR: ≤ 5% myeloblasts with normal maturation of all cell lines and return to normal cellularity; osteomyelofibrosis was absent or equal to mild reticulin fibrosis; resolution of extramedullary disease present before therapy.
PR: normalization of peripheral counts and hepatosplenomegaly with bone marrow blasts reduced by 50% but >5% of cellularity except in cases of MDS/MPN with ≤ 5% blasts at baseline.
Measured: Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months
Event-free Survival
Measured: Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months
Maximum Plasma Concentration (Cmax) of AMG 176
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. Pharmacokinetic (PK) parameters were determined from the time concentration profile using noncompartmental analysis.
Measured: Cycle 1: pre-dose, end of infusion (EOI), 3, 5, 7, 8, 24 hours post-infusion in weeks 1 and 2; pre-dose, EOI, 8 and 24 hours post-infusion in cycle 1 weeks 3 and 4
Time to Cmax (Tmax) of AMG 176
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
Measured: Cycle 1: pre-dose, EOI, 3, 5, 7, 8, 24 hours post-infusion in weeks 1 and 2; pre-dose, EOI, 8 and 24 hours post-infusion in cycle 1 weeks 3 and 4
Area Under the Plasma Concentration Time Curve From 0 to 168 Hours (AUC168hr) of AMG 176
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
Measured: Cycle 1: pre-dose, EOI, 3, 5, 7, 8, 24 hours post-infusion in weeks 1 and 2; pre-dose, EOI, 8 and 24 hours post-infusion in cycle 1 weeks 3 and 4
Terminal Half-life of AMG 176
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
Measured: Cycle 1: pre-dose, EOI, 3, 5, 7, 8, 24 hours post-infusion in weeks 1 and 2; pre-dose, EOI, 8 and 24 hours post-infusion in cycle 1 weeks 3 and 4
Clearance (CL) of AMG 176
AMG 176 plasma concentrations with values below the limit of quantification were set to zero. PK parameters were determined from the time concentration profile using noncompartmental analysis.
Measured: Cycle 1: pre-dose, EOI, 3, 5, 7, 8, 24 hours post-infusion in weeks 1 and 2; pre-dose, EOI, 8 and 24 hours post-infusion in cycle 1 weeks 3 and 4
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2022
- Study start14 Nov 2022
- Primary completion19 Dec 2023
- Study completion19 Dec 2023
Why it stopped: Sponsor decision, unrelated to safety
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 Higher Risk Myelodysplastic SyndromeStudies 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
- 7 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
- NCT05209152
- Sponsor's protocol ID
- 20200392
- Status last verified
- Jun 2025
- First submitted
- 13 Jan 2022
- Last updated
- 14 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- 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