Study of GDX012 in Patients With MRD Positive AML

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05001451
• Other study ID #: GDX012U-001
• Status: Terminated
• Phase: Phase 1
• Start date: August 13, 2021
• Est. completion date: June 3, 2022

Study information

• Verified date: July 2022
• Source: GammaDelta Therapeutics Limited
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 3
• Est. completion date: June 3, 2022
• Est. primary completion date: June 3, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
United States	City of Hope	Duarte	California

Sponsors (1)

Lead Sponsor	Collaborator
GammaDelta Therapeutics Limited

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment emergent adverse events (AEs) and serious adverse events (SAEs)	AEs and SAEs occurring following administration of GDX012	Up to 100 days
Primary	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
Primary	Incidence of dose limiting toxicities (DLTs)	DLTs occurring following administration of GDX012, measured using CTCAE 5.0 criteria	Up to 100 days
Primary	Establish the maximum tolerated dose (MTD) of GDX012		Up to 100 days
Secondary	Evaluate the antileukemic activity of GDX012	Minimal residual disease (MRD) assessed by flow cytometry	Up to 1 year
Secondary	Evaluate the antileukemic activity of GDX012	Incidence of patients converting from MRD positive to MRD negative	Up to 1 year
Secondary	Evaluate the antileukemic activity of GDX012	Progression-free survival (PFS) and overall survival (OS)	Up to 1 year