Safety, Tolerability, PK/PD of FE 203799 in Adults With Lymphomas
Status:
Withdrawn
Trial end date:
2019-03-31
Target enrollment:
Participant gender:
Summary
RATIONALE:
The integrity of the intestinal mucosa is a key factor for the preservation of a normal gut
function. Damage of the epithelium (i.e. by chemotherapy) results in significant cellular and
molecular alterations that ultimately lead to intestinal dysfunction/failure. This intestinal
dysfunction manifests as several pathological processes, such as inability to absorb
nutrients, intestinal inflammation, immune system dysregulation, and disequilibrium of normal
intestinal microbiota leading to increased risk of infection due to bacterial translocation
and septicaemia. Gastrointestinal (GI) mucositis is a well-known, frequent and debilitating
side effect of most anticancer regimens with a very high incidence in hemato-oncology. The
most common symptoms are nausea, vomiting, weight loss, abdominal cramps and pain, diarrhea,
and electrolyte imbalance. Patients may also experience ulceration/bleeding and injury of the
lining of the entire gastrointestinal tract from the esophagus to the colon. Currently no
therapy is available for the prevention or treatment of GI intestinal injury. Treatment of
related symptoms is limited to supportive measures to decrease diarrhea and to preventive
antibiotic therapy. The GLP-2 analogue, FE 203799, has a favorable pharmacology profile for
clinical development in the intended therapeutic indication of myeloablative
chemotherapy-induced GI damage. The data collected from animal studies has shown that FE
203799 stimulates the proliferation of the intestinal epithelium and protects the GI mucosa
from chemotherapy-induced injury. Hence, the primary pharmacologic activity of FE 203799
would promote a healthy GI microenvironment, thus preventing intestinal dysfunction and
related complications.
PURPOSE: Prevention by FE 203799 of chemotherapy-induced intestinal damage and related
complications in patients with lymphoma receiving Melphalan based (BEAM) myeloablative
conditioning regimen followed by hematopoietic stem cell transplantation.