A Phase I/II Dose Schedule Finding Study of ch14.18/CHO Continuous Infusion Combined With Subcutaneous Aldesleukin (IL-2) in Patients With Primary Refractory or Relapsed Neuroblastoma
Although a lot of children and young people with neuroblastoma can be cured with current
standard chemotherapy, sometimes, particularly at relapse the disease no longer responds to
standard drugs. Therefore, there is a need to find new drug combinations which will act
against neuroblastoma which no longer responds to standard drugs.
Ch14.18/CHO has been shown to improve the outcome of patients with neuroblastoma. However,
one of the side effects of receiving ch14.18/CHO is severe pain. High doses of intravenous
morphine are needed to control the pain and this means that patients must stay in hospital.
Results from other clinical trials have shown that giving ch14.18/CHO over a longer time
reduces pain, yet the drug still works just as well to fight the neuroblastoma. The
clinical trial aims to give ch14.18/CHO over a longer time so that intravenous morphine is
not needed and that this treatment regimen can ultimately be given in an outpatient setting.
Ch14.18/CHO is a monoclonal antibody. Monoclonal antibodies are made in the laboratory and
are designed to bind to specific cancer cells. Ch14.18/CHO was designed to bind to
neuroblastoma cells and other cancer cells that express the GD-2 antigen. The GD-2 antigen
is expressed by virtually all neuroblastoma cells. An antigen is a substance that
stimulates an immune response in the body by producing antibodies. Thus, when ch14.18/CHO
binds to the neuroblastoma cells, the body's immune system is stimulated to attack and kill
the neuroblastoma cells. Ch14.18/CHO is called chimeric, because it was genetically
engineered to consist of 30% mouse-protein and of 70% human protein.
Ch14.18/CHO represents a new kind of cancer therapy that, unlike chemotherapy and radiation,
targets the destruction of cancer cells without destroying nearby healthy cells. There is
laboratory evidence to suggest that ch14.18/CHO can activate the body's own immune cells to
destroy cancer cells. These immune cells include killer cells that are activated or
stimulated by aldesleukin (IL-2). Therefore this treatment is a combination of ch14.18/CHO
and aldesleukin (IL-2).
Aldesleukin (IL-2) is a substance that is similar to a substance made by the body in all
individuals. Under normal circumstances, the body makes small amounts of aldesleukin (IL-2)
that help white blood cells fight infection. It is now possible to make aldesleukin (IL-2)
in the laboratory and give humans much higher doses than their own body makes. There is
evidence in the laboratory and in animals that aldesleukin (IL-2) increases the anti-cancer
effect of monoclonal antibodies like ch14.18/CHO. We wish to study whether aldesleukin
(IL-2) can help improve the effectiveness of ch14.18/CHO in humans.
In addition to ch14.18/CHO and aldesleukin (IL-2), isotretinoin (13-cis-RA) will also be
given. Isotretinoin (13-cis-RA) is considered standard treatment for patients with
neuroblastoma and works by induction of neuroblastoma cell death.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
On day 15 of the first cycle in ≥ 80% of patients: an increase of 500% and/or an absolute minimum increase to ≥100 cells/mcLof the CD16/CD56 positive activated NK cells, AND a measurable ch14.18/CHO level of at least 1 µg/ml.
day 15 of first cycle
Holger Lode, MD, PhD
Austria: Agency for Health and Food Safety