A Phase III Randomized, Double-Blind Trial to Evaluate the Efficacy of Uproleselan Administered with Chemotherapy versus Chemotherapy Alone in Patients with Relapsed/Refractory Acute Myeloid Leukemia.
Dr Gavin Cull
Acute Myeloid Leukaemia (AML)
The bone marrow is like a factory, producing all types of blood cells. This process begins with immature stem cells in the bone marrow, and results in production of mature red cells, platelets and different types of white cells.
Acute myeloid leukaemia (AML) is an aggressive cancer of the bone marrow. In AML, there is an overproduction of immature white cells, known as blasts. These immature cells do not function properly to prevent and fight infection, and can result in production of inadequate numbers of red cells and platelets, which in turn may lead to anaemia, bleeding and bruising.
A molecule called E-selectin, with a variety of functions, is expressed in the circulatory system during periods of inflammation and stress and is permanently expressed in the bone marrow. In people with AML, blast cells have potential to bind to E-selectin within the bone marrow, and may encourage resistance of the leukaemia to chemotherapy. The presence of E-selectin in the circulation can also contribute to some chemotherapy side effects (eg. sore mouth, known as mucositis).
Uproleselan (GMI-1271) is a drug which works as an E-selectin inhibitor. It prevents binding of the AML blast cells to E-selectin, and inhibits the activity of E-selectin in the circulation. It thereby potentially increases sensitivity and response of the AML to chemotherapy treatment, and potentially reduces some chemotherapy side effects. The safety of Uproleselan has already been established in early phase clinical trials.
The purpose of this study is investigate whether the addition of Uproleselan to standard chemotherapy regimens improves outcomes for patients with AML that has not responded to previous treatment, or that has returned following previous successful treatment. Patients on the study will be randomised once enrolled on the trial to receive either standard chemotherapy treatment, or to receive chemotherapy plus the addition of Uproleselan.
Include, but not limited to, the following:
- ≥18 years and ≤75 years in age
- Patients with relapsed or refractory AML
- No more than one prior stem cell transplant
- Has not received the chemotherapy regimen to be used for induction on this trial
- Is considered medically eligible to receive the chemotherapy regimen to be used for induction on this trial
- Patients with acute promyelocytic leukemia, acute leukemia of ambiguous lineage (biphenotypic leukemia), chronic myeloid leukemia with myeloid blast crisis, or secondary refractory AML.
Active signs or symptoms of CNS involvement by malignancy.
- Stem cell transplantation ≤4 months prior to dosing.
- Any immunotherapy or radiotherapy therapy within 28 days of dosing; any other experimental therapy or chemotherapy within 14 days of dosing.
Prior use of G-CSF, CM-CSF or plerixafor within 7 days of dosing.
- Inadequate organ function.
- Abnormal liver function.
- Known active infection with hepatitis A, B, or C, or human immunodeficiency virus.
- Moderate kidney dysfunction (glomerular filtration rate <45 mL/min).
- Uncontrolled acute life-threatening bacterial, viral, or fungal infection.
- Clinically significant cardiovascular disease.
- Major surgery within 4 weeks of dosing.