NCT05209152 · REGISTRY CONDITION SEARCH

AMG 176 With Azacitidine in Subjects With Myelodysplastic Syndrome /Chronic Myelomonocytic Leukemia

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: TERMINATED
Registry last update: 2025-07-14

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).

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)

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outcome · POSTED

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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outcome · POSTED

Number of Participants With a Response According to the Uniform Response Criteria for MDS/Myeloproliferative Neoplasm (MPN)

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outcome · POSTED

Time to a Response According to the Uniform Response Criteria for MDS/MPN

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outcome · POSTED

Duration of Response According to the Uniform Response Criteria for MDS/MPN

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outcome · POSTED

Event-free Survival

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outcome · POSTED

Maximum Plasma Concentration (Cmax) of AMG 176

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outcome · POSTED

Time to Cmax (Tmax) of AMG 176

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outcome · POSTED

Area Under the Plasma Concentration Time Curve From 0 to 168 Hours (AUC168hr) of AMG 176

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outcome · POSTED

Terminal Half-life of AMG 176

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outcome · POSTED

Clearance (CL) of AMG 176

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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 a. 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: 1. 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; 2. 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 Exclusion Criteria: * 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
healthy Volunteers: false
maximum Age: 85 Years
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
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).
intervention Names
Drug: AMG 176
label
Part 1A - AMG 176 Monotherapy (Dose Exploration)
type
EXPERIMENTAL
description
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.
intervention Names
Drug: AMG 176
Drug: Azacitidine
label
Part 1B - AMG 176 and Azacitidine Combination Therapy (Dose Exploration)
type
EXPERIMENTAL
description
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.
intervention Names
Drug: AMG 176
Drug: Azacitidine
label
Part 2 - AMG 176 and Azacitidine Combination Therapy (Dose Expansion)
type
EXPERIMENTAL

interventions

arm Group Labels
Part 1A - AMG 176 Monotherapy (Dose Exploration)
Part 1B - AMG 176 and Azacitidine Combination Therapy (Dose Exploration)
Part 2 - AMG 176 and Azacitidine Combination Therapy (Dose Expansion)
description
Administered as an intravenous (IV) infusion.
name
AMG 176
type
DRUG
arm Group Labels
Part 1B - AMG 176 and Azacitidine Combination Therapy (Dose Exploration)
Part 2 - AMG 176 and Azacitidine Combination Therapy (Dose Expansion)
description
Administered as an IV infusion or subcutaneous (SC) injection.
name
Azacitidine
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

SEQUENTIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 7
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)
time Frame
Day 1 to day 28 of cycle 1 (each cycle was 28 days)
description
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.
measure
Number of Participants With Treatment-emergent Adverse Events (TEAEs)
time Frame
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

description
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.
measure
Number of Participants With a Response According to the Uniform Response Criteria for MDS/Myeloproliferative Neoplasm (MPN)
time Frame
Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months
description
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.
measure
Time to a Response According to the Uniform Response Criteria for MDS/MPN
time Frame
Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months
description
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.
measure
Duration of Response According to the Uniform Response Criteria for MDS/MPN
time Frame
Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months
measure
Event-free Survival
time Frame
Cycle 1 to disease progression or end of study, whichever occurred earlier (cycle length = 28 days). Median time on study was 4.1 months
description
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.
measure
Maximum Plasma Concentration (Cmax) of AMG 176
time Frame
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
description
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.
measure
Time to Cmax (Tmax) of AMG 176
time Frame
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
description
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.
measure
Area Under the Plasma Concentration Time Curve From 0 to 168 Hours (AUC168hr) of AMG 176
time Frame
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
description
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.
measure
Terminal Half-life of AMG 176
time Frame
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
description
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.
measure
Clearance (CL) of AMG 176
time Frame
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

Full study description

brief 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).
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.

Source references