A Phase I/II Trial of Recombinant-Methionyl Human Stem Cell Factor (SCF) in Adult Patients With Sickling Disorders
Status:
Completed
Trial end date:
2000-10-01
Target enrollment:
Participant gender:
Summary
Sickle cell anemia is a genetic disorder that results from a single nucleotide substitution
in codon 6 of the beta-globin gene which, in the homozygous state, produces an abnormal
hemoglobin that is prone to polymer formation when deoxygenated. The polymerized hemoglobin
leads to impaired deformability and sickling of red blood cells which subsequently lodge in
end-arterioles producing the classic and most prominent feature of the disorder, repeated
vasoocclusive crises. Despite knowledge of the precise genetic defect for decades, only
recently has there been therapeutic impact based upon this knowledge when a clear benefit
from treatment with hydroxyurea, a cell cycle-specific agent administered to induce
production of fetal hemoglobin (HbF) by stimulating gamma-globin synthesis, was reported in
patients with sickle cell disease (SCD). The reduction in the frequency and severity of
vasoocclusive crises seen has been attributed to the increase in HbF levels in responsive
patients. While the majority of patients demonstrate a rise in HbF, not all such patients
benefit from treatment. Given these results, alternative agents that also stimulate the
production of HbF warrant investigation in the treatment of SCD. Recombinant-methionyl human
stem cell factor (SCF) is a hematopoietic growth factor with activity on immature
hematopoietic progenitor cells. SCF stimulates the production of HbF in vitro and in vivo,
and this effect is attainable without the myelosuppression associated with hydroxyurea. In
this phase I/II trial, we will administer SCF in a dose escalating fashion to patients with
sickling disorders. Parameters to be measured are HbF levels, F cell levels, peripheral blood
CD34 levels, frequency, duration, and severity of vasoocclusive crises, and toxicity.
Phase:
Phase 1
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)