Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00005783
Recruitment Status : Completed
First Posted : December 10, 2002
Last Update Posted : March 4, 2008
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE June 3, 2000
First Posted Date  ICMJE December 10, 2002
Last Update Posted Date March 4, 2008
Study Start Date  ICMJE March 2000
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00005783 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Phase I/II Trial of Recombinant-Methionyl Human Stem Cell Factor (SCF) in Adult Patients With Sickling Disorders
Official Title  ICMJE A Phase I/II Trial of Recombinant-Methionyl Human Stem Cell Factor (SCF) in Adult Patients With Sickling Disorders
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.
Detailed Description 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE
  • Hemoglobin SC Disease
  • Sickle Cell Anemia
Intervention  ICMJE Drug: Recombinant-methionyl human stem cell factor
Study Arms  ICMJE Not Provided
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: June¬†29,¬†2006)
50
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE October 2000
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00005783
Other Study ID Numbers  ICMJE 000087
00-DK-0087
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date February 2000

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP