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

Study Overview
=================
Brief Summary
-----------------
The purpose of this First-in-Human Phase 1 study is to determine if AMG 330 given as a continuous IV infusion is safe and tolerable in adult subjects that have myeloid malignancies, and to determine the maximum tolerated dose and/or a biologically active dose. The study will be conducted in multiple sites and test increasing doses of AMG 330. The safety of subjects will be monitored by intensive assessment of vital signs, electrocardiograms, physical examinations, and laboratory tests.

Official Title
-----------------
A Phase 1 First-in-human Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of AMG 330 Administered as Continuous Intravenous Infusion in Subjects With Myeloid Malignancies

Conditions
-----------------
Relapsed/Refractory AML, Minimal Residual Disease Positive AML, Myelodysplastic Syndrome

Intervention / Treatment
-----------------
* Drug: AMG 330


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Informed consent provided 18 years or older Relapsed/refractory AML: AML as defined by the WHO Classification persisting or recurring following one or more treatment courses except promyelocytic leukemia (APML) Exclusion criteria: Active extramedullary AML in testes or central nervous system (CNS) Known hypersensitivity to immunoglobulins or to any other component of the IP formulation (eg, sucrose, captisol, potassium, polysorbate 80, citrate, lysine) Prior malignancy (other than in situ cancer) unless treated with curative intent and without evidence of disease for > 1 years before screening

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1: Relapsed/Refractory Acute Myeloid Leukemia (R/R AML)<br> | Drug: AMG 330<br>* 0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.<br>|
| Experimental: Group 2: Minimal Residual Disease Positive (MRD+) AML<br> | Drug: AMG 330<br>* 0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.<br>|
| Experimental: Group 3: Myelodysplastic syndrome (MDS)<br> | Drug: AMG 330<br>* 0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.<br>|
| Experimental: Group 4: R/R AML with alternative pretreatment<br> | Drug: AMG 330<br>* 0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.<br>|
| Experimental: Group 5: R/R AML with alternative dose schedule<br> | Drug: AMG 330<br>* 0.5 µg/day - 1.6 mg/day cIV infusion administered in cycles from 14 to 28 days.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subject incidence of adverse events (AEs) as a measure of safety |  | 36 months | 
| Subject incidence of dose-limiting toxicities (DLTs) as a measure of safety |  | 36 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of anti-AMG 330 antibody formation |  | 36 months | 
| Efficacy parameter: Response rate in subjects with relapsed/refractory acute myeloid leukemia |  | 36 months | 
| Efficacy parameter: Response rate in subjects with myelodysplastic syndrome |  | 36 months | 
| Efficacy parameter: Response rate in subjects with minimal residual disease (MRD) positive acute myeloid leukemia |  | 36 months | 
| Efficacy parameter: Duration of response |  | 36 months | 
| Efficacy parameter: Time to progression |  | 36 months | 
| Efficacy parameter: Time to response |  | 36 months | 
| Pharmacokinetic parameter: Half-life of AMG 330 |  | 32 months | 
| Pharmacokinetic parameter: Steady state concentration of AMG 330 |  | 32 months | 
| Pharmacokinetic parameter: Volume of distribution of AMG 330 |  | 32 months | 
| Pharmacokinetic parameter: Clearance of AMG 330 |  | 32 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Amgen, Phase 1, Clinical Trial, Oncology/Hematology, Relapsed/Refractory AML, Immunotherapy