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

NCT ID: NCT05209152

Last Updated: 2025-07-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 7 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-14
• Study Completion Date: 2023-12-19

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.

Conditions

Higher Risk Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1A - AMG 176 Monotherapy (Dose Exploration)

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).

Group Type: EXPERIMENTAL

AMG 176

Intervention Type: DRUG

Administered as an intravenous (IV) infusion.

Part 1B - AMG 176 and Azacitidine Combination Therapy (Dose Exploration)

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.

Group Type: EXPERIMENTAL

AMG 176

Intervention Type: DRUG

Administered as an intravenous (IV) infusion.

Azacitidine

Intervention Type: DRUG

Administered as an IV infusion or subcutaneous (SC) injection.

Part 2 - AMG 176 and Azacitidine Combination Therapy (Dose Expansion)

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.

Group Type: EXPERIMENTAL

AMG 176

Intervention Type: DRUG

Administered as an intravenous (IV) infusion.

Azacitidine

Intervention Type: DRUG

Administered as an IV infusion or subcutaneous (SC) injection.

Interventions

AMG 176

Administered as an intravenous (IV) infusion.

Intervention Type: DRUG

Azacitidine

Administered as an IV infusion or subcutaneous (SC) injection.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

MD

Role: STUDY_DIRECTOR

Amgen

Locations

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

20200392

Identifier Type: -

Identifier Source: org_study_id