A Phase 1 Study of AMG 330 in Subjects With Myeloid Malignancies

JRCT ID: jRCT2071210044

Registered date:19/07/2021

Basic Information

• Recruitment status: Complete
• Health condition(s) or Problem(s) studied: Relapsed/Refractory AML, Minimal Residual Disease Positive AML, Myelodysplastic Syndrome
• Date of first enrollment: 31/08/2015
• Target sample size: 256
• Countries of recruitment: United States,Japan,Germany,Japan,Netherlands,Japan,Canada,Japan
• Study type: Interventional

Intervention(s)

Experimental: Group 1: Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)
Experimental: Group 2: Minimal Residual Disease Positive (MRD+) AML
Experimental: Group 3: Myelodysplastic syndrome (MDS)
Experimental: Group 4: R/R AML with alternative pretreatment
Experimental: Group 5: R/R AML with alternative dose schedule

0.5 ug/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.

Outcome(s)

Primary Outcome

1. Number of Participants Who Experienced a Dose-limiting Toxicity (DLT) [Time Frame: Day 1 to Day 14]
A participant was not DLT-evaluable if they dropped out before completion of the DLT window (14 days) for reasons other than an adverse event related to study drug or the participant had not received investigational product (IP) treatment for at least 14 days at the target dose for a 3- or 4-week cycle or at least 7 days at a target dose for a 2- week cycle. Furthermore, following drug interruptions, if a participant was unable to complete 2 repeat cycles for reasons other than DLT, the participant was not DLT evaluable.
2. Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE) [Time Frame: Day 1 until 30 days after last dose. Median duration of treatment was: Group 1 - 29.0 days; Group 2 - 29.0 days; Group 3 - 49.50 days; Group 4 - 23.50 days]
The severity of TEAEs were graded using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. The general guideline for assessment ranged from Grade 1 to 5, with higher grades indicating a worse outcome, and included: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death.

Secondary Outcome

1. Number of Participants Who Experienced an Incident of Anti-AMG 330 Antibody Formation [Time Frame: Baseline until the end of study, up to approximately 6 months]
Number of participants with a binding anti-body positive result at any timepoint post-baseline who had a negative or no result at baseline.
2. Response Rate in Participants With R/R AML [Time Frame: From first dose of IP (Day 1) until the end of study, up to approximately 6months]
Response for participants with R/R AML was defi ned as the percentage of participants with complete response (CR)/complete remission with incomplete count recovery (CRi)/morphologic leukemia-free state (MLFS) [per modified international working group (IWG) criteria] or complete remission with partial hematologic recovery (CRh).
3. Response Rate in Participants With MRD-positive AML [Time Frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months]
Response for participants with MRD-positive AML was defined as the percentage of participants with a conversion from MRD+ status with 0.1% threshold to CRMDR- or CRiMD-.
4. Response Rate in Participants With MDS [Time Frame: From first dose of IP (Day 1) until the end of study, up to approximately 6 months]
Response for participants with MDS was defined as the percentage of participants with CR or marrow complete remission per IWG.
5. Duration of Response [Time Frame: From fi rst dose of IP (Day 1) until the end of study, up to approximately 6 months]
Duration of response was defi ned as the interval from the date of the fi rst disease assessment indicating an overall response to the first documented relapse, disease progression, or death due to any cause, whichever occurs first.
6. Time to Response [Time Frame: From fi rst dose of IP (Day 1) until the end of study, up to approximately 6 months]
Time to response was defi ned as the interval from the first administration of AMG 330 to the fi rst documentation of response.
7. Event-free Survival [Time Frame: From fi rst dose of IP (Day 1) until the end of study, up to approximately 6 months]
Event-free survival was defined as the interval from fi rst administration of AMG 330 to the earliest of date of treatment failure, relapse for responders, or death due to any cause.
8. Overall Survival [Time Frame: Baseline until the end of study, up to approximately 6 months]
Overall survival was defi ned as the time from enrollment until death due to any cause.
9. 14 Day Infusion Duration: Terminal Half Life (t1/2 z) of AMG 330 [Time Frame: 14 day infusion duration: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)]
10. 28 Day Infusion Duration: t1/2 z of AMG 330 [Time Frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30of Cycle 1 (each cycle was 36 days)]
11. 14 Day Infusion Duration: Steady State Serum Concentration After End of Infusion (Css) of AMG 330 [Time Frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28days)]
12. 28 Day Infusion Duration: Css After End of Infusion of AMG 330 [Time Frame: Pre-dose to 48 hours from the start of infusion, and days 8,15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)]
13. 14 Day Infusion Duration: Volume of Distribution at Steady State (Vz) of AMG 330 [Time Frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)]
14. 28 Day Infusion Duration: Vz of AMG 330 [Time Frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 ofCycle 1 (each cycle was 36 day)]
15. 14 Day Infusion Duration: Clearance at Steady State (CL) for AMG 330 [Time Frame: Pre-dose to 48 hours from the start of infusion, and days 4, 8, 11, 15, 16 and 22 of Cycle 1 for Group 1 and days 8, 15 and 16 for Group 4 (each cycle was 28 days)]
16. 28 Day Infusion Duration: CL of AMG 330 [Time Frame: Pre-dose to 48 hours from the start of infusion, and days 8, 15, 22, 29, and 30 of Cycle 1 (each cycle was 36 days)]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Informed consent provided
2. 18 years or older
3. Relapsed/refractory AML: AML as defined by the WHO Classification persisting or recurring following one or more treatment courses except promyelocytic leukemia (APML)

Exclude criteria

1. Active extramedullary AML in testes or central nervous system (CNS)
2. Known hypersensitivity to immunoglobulins or to any other component of the IP formulation (eg, sucrose, captisol, potassium, polysorbate 80, citrate, lysine)
3. Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for more than 1 years before screening

Related Information

• Primary Sponsor: Contact Local
• Secondary ID(s): NCT02520427