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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

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

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

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

Learn more about this trial

Study of GDX012 in Patients With MRD Positive AML

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