Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor ALL

Study Overview
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Brief Summary
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The primary objective of this phase 1b study is to evaluate the safety and tolerability of blinatumomab and AMG 404 in combination in adults with R/R B-ALL and to estimate the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of AMG 404 when combined with continuous intravenous infusion (cIV) blinatumomab.

Official Title
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A Phase 1b Open-label Study Investigating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Administration of Blinatumomab in Combination With AMG 404 for the Treatment of Adults With Relapsed or Refractory B Cell Precursor Acute Lymphoblastic Leukemia (ALL)

Conditions
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Acute Lymphoblastic Leukemia

Intervention / Treatment
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* Drug: Blinatumomab
* Drug: AMG 404
* Drug: Dexamethasone Premedication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Age ≥ 18 years at enrollment. Greater than or equal to 5% blasts in the bone marrow. Eastern Cooperative Oncology Group performance status (ECOG PS) ≤ 2. Negative pregnancy test in women of childbearing potential. Exclusion Criteria Cancer chemotherapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy) within 14 days prior to study Day 1. Known hypersensitivity to blinatumomab or AMG 404 or to any component of the product formulation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Blinatumomab and AMG 404<br> | Drug: Blinatumomab<br>* Blinatumomab will be administered as a continuous intravenous infusion (cIV).<br>* Other names: Blincyto;Drug: AMG 404<br>* AMG 404 will be administered as an intravenous infusion (IV).<br>Drug: Dexamethasone Premedication<br>* Dexamethasone will be administered orally or intravenously prior to blinatumomab treatment, as needed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants who Experience Dose-Limiting Toxicities (DLTs) |  | Up to 8 Weeks | 
| Number of Participants who Experience Treatment-Emergent Adverse Events (TEAEs) |  | Up to 51 Weeks | 
| Number of Participants who Experience Serious Treatment-Emergent Adverse Events |  | Up to 51 Weeks | 
| Number of Participants who Experience Treatment-Related Treatment-Emergent Adverse Events |  | Up to 51 Weeks | 
| Number of Participants who Experience Adverse Events of Interest (EOI) |  | Up to 51 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Complete Remission (CR) Including Complete Remission with Partial Hematological Recovery (CRh*) |  | Up to 51 Weeks | 
| Complete Remission (CR) Rate |  | Up to 51 Weeks | 
| Duration of Complete Remission (CR) |  | Up to 51 Weeks | 
| Duration of Complete Remission (CR) or Complete Remission with Partial Hematological Recovery (CRh*) |  | Up to 51 Weeks | 
| Steady State Concentrations (Css) of Blinatumomab |  | Up to 35 Weeks | 
| Maximum Observed Concentration (Cmax) of AMG 404 |  | Up to 51 Weeks | 
| Time to Maximum Observed Concentration (Tmax) of AMG 404 |  | Up to 51 Weeks | 
| Area Under the Plasma Concentration-Time Curve (AUC) of AMG 404 |  | Up to 51 Weeks | 
| Number of Participants with Incidences of Anti-Blinatumomab Antibodies |  | Up to 35 Weeks | 
| Number of Participants with Incidences of Anti-AMG 404 Antibodies |  | Up to 35 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Blinatumomab, AMG 404, Leukemia