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

Primary Purpose

Hemoglobin SC Disease, Sickle Cell Anemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Recombinant-methionyl human stem cell factor
Sponsored by
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemoglobin SC Disease focused on measuring Fetal Hemoglobin, Hematopoietic Growth Factor, Peripheral Blood CD34 Cells, Vasoocclusive Crisis, Sickle Cell Anemia, Sickle Cell Disease, Sickle Cell Disorder

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

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

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
June 3, 2000
Last Updated
March 3, 2008
Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT00005783
Brief Title
A Phase I/II Trial of Recombinant-Methionyl Human Stem Cell Factor (SCF) in Adult Patients With Sickling Disorders
Official Title
A Phase I/II Trial of Recombinant-Methionyl Human Stem Cell Factor (SCF) in Adult Patients With Sickling Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
February 2000
Overall Recruitment Status
Completed
Study Start Date
March 2000 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
October 2000 (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Enrollment
50 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Recombinant-methionyl human stem cell factor

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Facility Information:
Facility Name
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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