Study of GDX012 in Patients With MRD Positive AML

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

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.

Study Overview

• Status: Terminated
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Biological: GDX012 Suspension for IV Infusion

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GammaDelta Therapeutics Limited
• Investigators: Study Director: Michael Koslowski, MD, GammaDelta Therapeutics Limited

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2021
• Primary Completion (Actual): June 3, 2022
• Study Completion (Actual): June 3, 2022

Study Registration Dates

• First Submitted: July 5, 2021
• First Submitted That Met QC Criteria: August 4, 2021
• First Posted (Actual): August 12, 2021

Study Record Updates

• Last Update Posted (Actual): July 20, 2022
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: AML; cell therapy; allogeneic; MRD; gamma delta T-cells
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: GDX012U-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No