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Terminated/Withdrawn
Sponsor ID
20200392

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

Sponsor ID
20200392
Clinicaltrials.gov ID
NCT05209152
EUCTIS ID
N/A
EudraCT ID
N/A
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Study Details

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).

Additional Study Details

Phase
Phase 1
Product
AMG 176
Type
Interventional
Masking
None (Open Label)
Enrollment
7
Additional Study Details

Protocol Summary

Primary Outcome Measures

Part 1A and 1B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)

Timeframe: Day 1 to Day 28

Part 1A and 1B: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)

Timeframe: Up to 1.5 years

Part 2: Overall Response Rate (ORR)

Timeframe: Up to 1.5 years

Secondary Outcome Measures

Part 1A and Part 1B: Overall Response

Timeframe: Up to 1.5 years

Part 1A, Part 1B and Part 2: Event-free Survival (EFS)

Timeframe: Up to 1.5 years

Part 1A and Part 1B: Time to Response (TTR)

Timeframe: Up to 1.5 years

Part 1A, Part 1B and Part 2: Duration of Response (DoR)

Timeframe: Up to 1.5 years

Part 1A: Maximum Concentration (Cmax) of AMG 176 when Administered as Monotherapy

Timeframe: 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

Part 1A: Area Under the Concentration-time Curve (AUC) of AMG 176 when Administered as Monotherapy

Timeframe: 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

Part 1A: Clearance (CL) of AMG 176 when Administered as Monotherapy

Timeframe: 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

Part 1A: Half-life (t1/2) of AMG 176 when Administered as Monotherapy

Timeframe: 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

Part 1B and Part 2: Cmax of AMG 176 when Administered in Combination

Timeframe: 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

Part 1B and Part 2: AUC of AMG 176 when Administered in Combination

Timeframe: 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

Part 1B and Part 2: CL of AMG 176 when Administered in Combination

Timeframe: 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

Part 1B and Part 2: T1/2 of AMG 176 when Administered in Combination

Timeframe: 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

Part 1B and Part 2: Cmax of Azacitidine when Administered in Combination

Timeframe: Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.

Part 1B and Part 2: AUC of Azacitidine when Administered in Combination

Timeframe: Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.

Part 1B and Part 2: CL of Azacitidine when Administered in Combination

Timeframe: Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.

Part 1B and Part 2: T1/2 of Azacitidine when Administered in Combination

Timeframe: Cycle 1 (=23 days) Day 1: Pre-dose, 5 mins post-dose, 30 mins post-dose, 1, 2, 4, and 8 hours post-dose.

Part 2: Time to Transformation to Acute Myeloid Leukemia (AML)

Timeframe: Up to 1.5 years

Part 2: Overall Survival (OS)

Timeframe: Up to 1.5 years

Part 2: Time to Next MDS Treatment (TTNT)

Timeframe: Up to 1.5 years

Locations

Location
Status
Contact Us
Location
University of Texas MD Anderson Cancer Center
Houston, TX, United States, 77030
Status
Recruiting
Study Info
Age
18 - 85 Years
Condition
  • Myelodysplastic Syndrome
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  • Leukemia
    • Sex
    All
    Trial Dates
    Nov 2022 - Dec 2023
    Inclusion and Exclusion 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: a. 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; b. 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