A Phase I/II Trial of Recombinant-Methionyl Human Stem Cell NCT00005783

Clinical Trial Details — Status: Completed

Administrative data
NCT number	NCT00005783
Other study ID #	000087
Secondary ID	00-DK-0087
Status	Completed
Phase	Phase 1
First received	June 3, 2000
Last updated	March 3, 2008
Start date	March 2000
Est. completion date	October 2000

Study information
Verified date	February 2000
Source	National Institutes of Health Clinical Center (CC)
Contact	n/a
Is FDA regulated	No
Health authority	United States: Federal Government
Study type	Interventional

Clinical Trial 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.

Description:

Recruitment information / eligibility
Status	Completed
Enrollment	50
Est. completion date	October 2000
Est. primary completion date
Accepts healthy volunteers	No
Gender	Both
Age group	N/A and older
Eligibility	INCLUSION CRITERIA: 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. No patients receiving hypertransfusion therapy. No current treatment (or within 2 weeks) with hematopoietic growth factors. No allergy to E. coli derived products. No history of seasonal or recurrent asthma within the 5 preceding years. No asthmatic symptoms (e.g. wheezing) related to a current respiratory tract infection. No other significant IgE-mediated hypersensitivities (including but not limited to allergic rhinitis, allergic eczema, anaphylactic reactions, congenital or acquired angioedema, and urticaria,). An isolated episode of urticaria occurring within the 5 years is not a contraindication. Patients with drug allergies manifested solely by rash are not excluded. No concurrent use of beta-adrenergic blocking agents. No concurrent use of monoamine oxidase inhibitors. No significant comorbid conditions including uncontrolled hypertension, congestive heart failure(greater NY class II), poorly controlled diabetes mellitus, and significant coronary artery disease with recent myocardial infarction or angioplasty (within the previous 6 months). No pregnancy, breast feeding, and unwillingness to use contraception. No concurrent use of other investigational products.

Study Design

Endpoint Classification: Safety Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

Intervention

Drug:
• Recombinant-methionyl human stem cell factor

Locations
Country	Name	City	State
United States	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)	Bethesda	Maryland

Sponsors *(1)*
Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States,

See also
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Terminated	`NCT01350232` - Treatment of Sickle Cell Anemia With Stem Cell Transplant	N/A
Withdrawn	`NCT00937144` - Endothelial Function in Patients With Sickle Cell Anemia Before and After Sildenafil	Phase 4
Completed	`NCT00512564` - Clinical and Laboratory Assessment of Iron Overload in Sickle Cell Anemia and Sickle Cell Thalassemia	N/A
Completed	`NCT00512226` - Iron Overload Assesment in Sickle Cell Anemia and Sickle Cell Thalassemia	N/A
Completed	`NCT00004143` - Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes	Phase 2
Completed	`NCT00004412` - Phase II Randomized Trial:Arginine Butyrate Plus Standard Local Therapy in Patients With Refractory Sickle Cell Ulcers	Phase 2
Withdrawn	`NCT01925001` - Phase 2 Study of MP4CO to Treat Vaso-occlusive Sickle Crisis	Phase 2
Completed	`NCT01783990` - Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) Follow-up Observational Study II Protocol
Completed	`NCT01848691` - Carbon Monoxide Monitor for the Measurement of End-Tidal Carbon Monoxide Levels in Children With or Without Hemolysis	N/A
Completed	`NCT00874172` - Effectiveness of New Analgesic Strategy Compared to the Usal Antalgic Strategy	N/A
Completed	`NCT01000155` - Efficacy of Vorinostat to Induce Fetal Hemoglobin in Sickle Cell Disease	Phase 2
Completed	`NCT00236093` - Extension Study of ACTIQ Treatment for Children and Adolescents With Breakthrough Pain	Phase 2
Completed	`NCT00399074` - Sulfadoxine- Pyrimethamine Versus Weekly Chloroquine for Malaria Prevention in Children With Sickle Cell Anemia	Phase 3
Completed	`NCT00004492` - Phase I/II Randomized Study of Hydroxyurea With or Without Clotrimazole in Patients With Sickle Cell Anemia	Phase 1/Phase 2

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

Clinical Trial Details — Status: Completed

Administrative data

Study information

Clinical Trial Summary

Description:

Recruitment information / eligibility

Study Design

Related Conditions & MeSH terms

Intervention

Locations

Sponsors (1)

Country where clinical trial is conducted