A Phase I/II Trial of Recombinant-Methionyl Human Stem Cell Factor (SCF) in Adult Patients With Sickling Disorders

NCT00005783 | Completed Phase 1

• 2 other identifiers: 00008700-DK-0087
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hemoglobin SC Disease; Sickle Cell Anemia

Keywords

Fetal Hemoglobin; Hematopoietic Growth Factor; Peripheral Blood CD34 Cells; Vasoocclusive Crisis; Sickle Cell Anemia; Sickle Cell Disease; Sickle Cell Disorder

Interventions

Recombinant-methionyl human stem cell factor DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with Hb SS, Sbeta-thal, SD, or SO-Arab
• Age greater than or equal to 18 years.
• Patient must have had a previous neurologic event (either symptomatic or found by imaging alone).
• More than one painful crises per year for the last 2 years, each requiring hospitalization.
• A previous acute chest syndrome.
• Evidence of renal damage but with a creatinine clearance of greater than 50 percent of normal.
• Red cell alloimmunization.
• Bilateral retinopathy.
• Osteonecrosis of multiple bones.
• Unilateral or bilateral leg ulcers.
• Patients who have failed a course of hydroxyurea or who have declined to take hydroxyurea.
• Able to give informed consent.
• No active sickle cell crises or acute chest syndrome.
• No active uncontrolled infection.
• No hydroxyurea, erythropoietin, and/or arginine butyrate therapy in the previous month.

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (1)

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Bethesda, Maryland, 20892, United States

Location

MeSH Terms

Conditions

Hemoglobin SC Disease; Anemia, Sickle Cell; beta-Thalassemia; Vaso-Occlusive Crises

Interventions

ancestim

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Thalassemia

Study Design

• Study Type: interventional
• Phase: phase 1
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: June 3, 2000
• First Posted: December 10, 2002
• Study Start: March 1, 2000
• Study Completion: October 1, 2000
• Last Updated: March 4, 2008

Record last verified: 2000-02

Locations

US (1)