Study of GDX012 in Patients With MRD Positive AML
Primary Purpose
Acute Myeloid Leukemia
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
GDX012 Suspension for IV Infusion
Sponsored by
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring AML, MRD, gamma delta T-cells, allogeneic, cell therapy
Eligibility Criteria
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.
Sites / Locations
- City of Hope
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
GDX012 Suspension for IV Infusion
Arm Description
Allogeneic cell therapy that is enriched for Vδ1+ γδ T cells
Outcomes
Primary Outcome Measures
Incidence of treatment emergent adverse events (AEs) and serious adverse events (SAEs)
AEs and SAEs occurring following administration of GDX012
Incidence of treatment emergent clinically significant abnormal laboratory assessments
Standard clinical laboratory assessments for organ function (i.e. heart, kidney, liver)
Incidence of dose limiting toxicities (DLTs)
DLTs occurring following administration of GDX012, measured using CTCAE 5.0 criteria
Establish the maximum tolerated dose (MTD) of GDX012
Secondary Outcome Measures
Evaluate the antileukemic activity of GDX012
Minimal residual disease (MRD) assessed by flow cytometry
Evaluate the antileukemic activity of GDX012
Incidence of patients converting from MRD positive to MRD negative
Evaluate the antileukemic activity of GDX012
Progression-free survival (PFS) and overall survival (OS)
Full Information
NCT ID
NCT05001451
First Posted
July 5, 2021
Last Updated
July 18, 2022
Sponsor
GammaDelta Therapeutics Limited
1. Study Identification
Unique Protocol Identification Number
NCT05001451
Brief Title
Study of GDX012 in Patients With MRD Positive AML
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2022
Overall Recruitment Status
Terminated
Why Stopped
This was a business decision to discontinue this clinical trial. The decision is not related to the safety of the investigational product, GDX012.
Study Start Date
August 13, 2021 (Actual)
Primary Completion Date
June 3, 2022 (Actual)
Study Completion Date
June 3, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GammaDelta Therapeutics Limited
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
AML, MRD, gamma delta T-cells, allogeneic, cell therapy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GDX012 Suspension for IV Infusion
Arm Type
Experimental
Arm Description
Allogeneic cell therapy that is enriched for Vδ1+ γδ T cells
Intervention Type
Biological
Intervention Name(s)
GDX012 Suspension for IV Infusion
Intervention Description
Biological: GDX012 Suspension for IV Infusion (single dose) following chemotherapy for lymphodepletion.
Drug: Fludarabine; chemotherapy for lymphodepletion
Drug: Cyclophosphamide; chemotherapy for lymphodepletion
Primary Outcome Measure Information:
Title
Incidence of treatment emergent adverse events (AEs) and serious adverse events (SAEs)
Description
AEs and SAEs occurring following administration of GDX012
Time Frame
Up to 100 days
Title
Incidence of treatment emergent clinically significant abnormal laboratory assessments
Description
Standard clinical laboratory assessments for organ function (i.e. heart, kidney, liver)
Time Frame
Up to 100 days
Title
Incidence of dose limiting toxicities (DLTs)
Description
DLTs occurring following administration of GDX012, measured using CTCAE 5.0 criteria
Time Frame
Up to 100 days
Title
Establish the maximum tolerated dose (MTD) of GDX012
Time Frame
Up to 100 days
Secondary Outcome Measure Information:
Title
Evaluate the antileukemic activity of GDX012
Description
Minimal residual disease (MRD) assessed by flow cytometry
Time Frame
Up to 1 year
Title
Evaluate the antileukemic activity of GDX012
Description
Incidence of patients converting from MRD positive to MRD negative
Time Frame
Up to 1 year
Title
Evaluate the antileukemic activity of GDX012
Description
Progression-free survival (PFS) and overall survival (OS)
Time Frame
Up to 1 year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Koslowski, MD
Organizational Affiliation
GammaDelta Therapeutics Limited
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of GDX012 in Patients With MRD Positive AML
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