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

Chronic Myelomonocytic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05209152
• Other study ID #: 20200392
• Status: Completed
• Phase: Phase 1
• Start date: November 14, 2022
• Est. completion date: December 19, 2023

Study information

• Verified date: April 2024
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• 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: 7
• Est. completion date: December 19, 2023
• Est. primary completion date: December 19, 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

Related Conditions & MeSH terms

• Chronic Myelomonocytic Leukemia
• Higher Risk Myelodysplastic Syndrome
• Leukemia
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

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

External Links

•   AmgenTrials clinical trials website