Study of GDX012 in Patients With MRD Positive AML

Study Overview
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Brief Summary
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The purpose of this first-in-human study is to assess the safety, tolerability, antileukemic activity and maximum tolerated dose (MTD) of GDX012 in AML patients who are MRD positive by multiparametric flow cytometry. The study will consist of a dose escalation stage to evaluate various doses of GDX012 after a lymphodepletion regimen comprising fludarabine and cyclophosphamide. Following determination of the MTD of GDX012, the study will expand at the MTD. Patients will be followed up for 12 months, after receiving GDX012.

Official Title
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A Phase 1, Open Label, Dose Escalation, and Dose Expansion Study to Assess the Safety, Tolerability, and Preliminary Antileukemic Activity of GDX012 in Patients With Minimal Residual Disease (MRD) Positive Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Biological: GDX012 Suspension for IV Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥ 18 years old Weight ≥ 40 kg Anticipated life expectancy > 3 months prior to lymphodepletion Karnofsky Performance Score ≥ 70% Histologically confirmed diagnosis of AML In complete response (CR) (including CRi/CRp); patients in first, second or subsequent CR (including CRi/CRp) are permitted MRD detected in bone marrow by MFC Negative pregnancy test (females of childbearing potential only) Agree to use effective birth control Left ventricular ejection fraction (LVEF) ≥ 50% Platelet Count ≥ 20 x 109/L Prothrombin Time or INR ≤ 1.5 x ULN (unless receiving therapeutic anticoagulation) Partial Thromboplastin Time ≤ 1.5 x ULN (unless receiving therapeutic anticoagulation) Hemoglobin ≥ 8.0 g/dL Creatinine Clearance ≥ 40mL/min Serum Total Bilirubin ≤ 1.5 x ULN (unless documented Gilbert's Syndrome with Direct Bilirubin < 35% of Total Bilirubin) ALT ≤ 2.5 x ULN Exclusion Criteria: Cytotoxic chemotherapy within 3 weeks Immune therapy within 4 weeks Immunosuppressive therapy within 2 weeks (with exceptions) Investigational treatment or interventional clinical trial within 4 weeks or 5 half-lives (if known), whichever is longer Major surgery within 4 weeks and/or not fully recovered from surgery-related toxicities Known hypersensitivity to chemotherapy, other agents, or excipients used in this study Female patient that is pregnant or lactating/breastfeeding Ongoing toxicity from prior anti-cancer therapy that have not recovered to ≤ Grade 1 (with exceptions) History of chronic or recurrent autoimmune or immune-mediated disease requiring steroids or other immunosuppressive treatments (including anti-tumor necrosis factor agents) Active CNS involvement (i.e. leukemic infiltration) Any other malignancy that requires active therapy Uncontrolled intercurrent illness (i.e. acute coronary syndrome in the last 6 months) Active infection with HIV, Hepatitis B or Hepatitis C NOTE: other protocol defined inclusion/exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GDX012 Suspension for IV Infusion<br>Allogeneic cell therapy that is enriched for Vδ1+ γδ T cells | Biological: GDX012 Suspension for IV Infusion<br>* Biological: GDX012 Suspension for IV Infusion (single dose) following chemotherapy for lymphodepletion. Drug: Fludarabine; chemotherapy for lymphodepletion Drug: Cyclophosphamide; chemotherapy for lymphodepletion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events (AEs) and serious adverse events (SAEs) | AEs and SAEs occurring following administration of GDX012 | Up to 100 days | 
| Incidence of treatment emergent clinically significant abnormal laboratory assessments | Standard clinical laboratory assessments for organ function (i.e. heart, kidney, liver) | Up to 100 days | 
| Incidence of dose limiting toxicities (DLTs) | DLTs occurring following administration of GDX012, measured using CTCAE 5.0 criteria | Up to 100 days | 
| Establish the maximum tolerated dose (MTD) of GDX012 |  | Up to 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the antileukemic activity of GDX012 | Minimal residual disease (MRD) assessed by flow cytometry | Up to 1 year | 
| Evaluate the antileukemic activity of GDX012 | Incidence of patients converting from MRD positive to MRD negative | Up to 1 year | 
| Evaluate the antileukemic activity of GDX012 | Progression-free survival (PFS) and overall survival (OS) | Up to 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allogeneic, AML, MRD, gamma delta T-cells, cell therapy