Acute Myeloid Leukemia
Conditions
Keywords
AML, MRD, gamma delta T-cells, allogeneic, cell therapy
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.
Interventions
BIOLOGICALGDX012 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
Sponsors
GammaDelta Therapeutics Limited
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment emergent adverse events (AEs) and serious adverse events (SAEs) | Up to 100 days | AEs and SAEs occurring following administration of GDX012 |
| Incidence of treatment emergent clinically significant abnormal laboratory assessments | Up to 100 days | Standard clinical laboratory assessments for organ function (i.e. heart, kidney, liver) |
| Incidence of dose limiting toxicities (DLTs) | Up to 100 days | DLTs occurring following administration of GDX012, measured using CTCAE 5.0 criteria |
| Establish the maximum tolerated dose (MTD) of GDX012 | Up to 100 days | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the antileukemic activity of GDX012 | Up to 1 year | Minimal residual disease (MRD) assessed by flow cytometry |
Countries
United States
Outcome results
None listed