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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT05209152
Other study ID # 20200392
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date November 14, 2022
Est. completion date December 8, 2023

Study information

Verified date January 2024
Source Amgen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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).


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.


Recruitment information / eligibility

Status Completed
Enrollment 9
Est. completion date December 8, 2023
Est. primary completion date December 8, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years to 85 Years
Eligibility 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
AMG 176
Administered as an intravenous (IV) infusion.
Azacitidine
Administered as an IV infusion or subcutaneous (SC) injection.

Locations

Country Name City State
United States University of Texas MD Anderson Cancer Center Houston Texas

Sponsors (1)

Lead Sponsor Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Part 1A and 1B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT) Day 1 to Day 28
Primary Part 1A and 1B: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) Up to 1.5 years
Primary Part 2: Overall Response Rate (ORR) As assessed according to the Uniform Response Criteria for Myelodysplastic/ Myeloproliferative Neoplasms (MDS/MPN). Up to 1.5 years
Secondary Part 1A and Part 1B: Overall Response As assessed according to the Uniform Response Criteria for MDS/MPN for R/R MDS/CMML participants. Up to 1.5 years
Secondary Part 1A, Part 1B and Part 2: Event-free Survival (EFS) Up to 1.5 years
Secondary Part 1A and Part 1B: Time to Response (TTR) Up to 1.5 years
Secondary Part 1A, Part 1B and Part 2: Duration of Response (DoR) Up to 1.5 years
Secondary Part 1A: Maximum Concentration (Cmax) of AMG 176 when Administered as Monotherapy Cycle 1 (=23 days) Day 1 and Day 8: Pre-dose and 0.5, 3, 5, 7, 8, 12 (Day 8 only) and 24 hours post-dose. Day 15 and 22: Pre-dose and 0.5, 8 and 24 hours post-dose. Cycle 2-4 (=23 days) Day 1: Pre-dose and 0.5 and 24 hours post-dose
Secondary Part 1A: Area Under the Concentration-time Curve (AUC) of AMG 176 when Administered as Monotherapy Cycle 1 (=23 days) Day 1 and Day 8: Pre-dose and 0.5, 3, 5, 7, 8, 12 (Day 8 only) and 24 hours post-dose. Day 15 and 22: Pre-dose and 0.5, 8 and 24 hours post-dose. Cycle 2-4 (=23 days) Day 1: Pre-dose and 0.5 and 24 hours post-dose
Secondary Part 1A: Clearance (CL) of AMG 176 when Administered as Monotherapy Cycle 1 (=23 days) Day 1 and Day 8: Pre-dose and 0.5, 3, 5, 7, 8, 12 (Day 8 only) and 24 hours post-dose. Day 15 and 22: Pre-dose and 0.5, 8 and 24 hours post-dose. Cycle 2-4 (=23 days) Day 1: Pre-dose and 0.5 and 24 hours post-dose
Secondary Part 1A: Half-life (t1/2) of AMG 176 when Administered as Monotherapy Cycle 1 (=23 days) Day 1 and Day 8: Pre-dose and 0.5, 3, 5, 7, 8, 12 (Day 8 only) and 24 hours post-dose. Day 15 and 22: Pre-dose and 0.5, 8 and 24 hours post-dose. Cycle 2-4 (=23 days) Day 1: Pre-dose and 0.5 and 24 hours post-dose
Secondary Part 1B and Part 2: Cmax of AMG 176 when Administered in Combination Cycle 1 (=23 days) Day 1 and Day 8: Pre-dose and 0.5, 3, 5, 7, 8, 12 (Day 8 only) and 24 hours post-dose. Day 15 and 22: Pre-dose and 0.5, 8 and 24 hours post-dose. Cycle 2-4 (=23 days) Day 1: Pre-dose and 0.5 and 24 hours post-dose
Secondary Part 1B and Part 2: AUC of AMG 176 when Administered in Combination Cycle 1 (=23 days) Day 1 and Day 8: Pre-dose and 0.5, 3, 5, 7, 8, 12 (Day 8 only) and 24 hours post-dose. Day 15 and 22: Pre-dose and 0.5, 8 and 24 hours post-dose. Cycle 2-4 (=23 days) Day 1: Pre-dose and 0.5 and 24 hours post-dose
Secondary Part 1B and Part 2: CL of AMG 176 when Administered in Combination Cycle 1 (=23 days) Day 1 and Day 8: Pre-dose and 0.5, 3, 5, 7, 8, 12 (Day 8 only) and 24 hours post-dose. Day 15 and 22: Pre-dose and 0.5, 8 and 24 hours post-dose. Cycle 2-4 (=23 days) Day 1: Pre-dose and 0.5 and 24 hours post-dose
Secondary Part 1B and Part 2: T1/2 of AMG 176 when Administered in Combination Cycle 1 (=23 days) Day 1 and Day 8: Pre-dose and 0.5, 3, 5, 7, 8, 12 (Day 8 only) and 24 hours post-dose. Day 15 and 22: Pre-dose and 0.5, 8 and 24 hours post-dose. Cycle 2-4 (=23 days) Day 1: Pre-dose and 0.5 and 24 hours post-dose
Secondary Part 1B and Part 2: Cmax of Azacitidine when Administered in Combination Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.
Secondary Part 1B and Part 2: AUC of Azacitidine when Administered in Combination Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.
Secondary Part 1B and Part 2: CL of Azacitidine when Administered in Combination Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.
Secondary Part 1B and Part 2: T1/2 of Azacitidine when Administered in Combination Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.
Secondary Part 2: Time to Transformation to Acute Myeloid Leukemia (AML) Up to 1.5 years
Secondary Part 2: Overall Survival (OS) Up to 1.5 years
Secondary Part 2: Time to Next MDS Treatment (TTNT) Up to 1.5 years
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