Status:
COMPLETED
Hematopoietic Stem Cell Transplantation Gene Therapy for Treatment of Severe Hemophilia A
Lead Sponsor:
Christian Medical College, Vellore, India
Collaborating Sponsors:
Dr. H. Trent Spencer, Professor, Emory University of Medicine, Atlanta Ga, 30322
Conditions:
Hemophilia A
Eligibility:
MALE
18-45 years
Phase:
PHASE1
Brief Summary
Factor VIII (FVIII) is a large plasma glycoprotein that participates in blood coagulation. Loss of circulating FVIII activity due to mutations within the F8 gene results in the X-linked, recessive ble...
Detailed Description
Eligible subjects will undergo (Cluster of Differentiation) CD34+ hematopoietic stem cell collection. These cells will be transduced ex vivo with (Cluster of Differentiation) CD68-ET3 lentiviral vecto...
Eligibility Criteria
Inclusion
- Able to provide informed consent for the protocol approved by the Institutional Review Board.
- Male subjects who are ≥18 years of age and \< 45 years of age.
- Diagnosis of severe hemophilia A (\<1 IU/dl factor VIII activity).
- Documented history of more than 100 exposures of factor VIII treatment.
- Average of at least 3 bleeds requiring treatment per year over the prior three years, at least 3 bleeds per year during the 3 years preceding the initiation of prophylaxis, or evidence of joint damage (knee, elbow or ankle) on physical or radiographic examination thought to be related to hemophilia.
- Performance status (Karnofsky score) of at least 70.
- Willing and able to comply with the requirements of the protocol.
Exclusion
- History of spontaneous central nervous system bleeding within the last 5 years.
- Significant organ dysfunction which could interfere with outcome of therapy such as: -
- Cardiac: There should be no evidence of significant cardiac dysfunction (resting left ventricular ejection fraction of \< 50%) and no cardiomegaly. There should not be uncontrollable hypertension.
- Renal: Glomerular Filtration Rate (GFR) \< 60 ml/min/1.73m2 as calculated using the Cockcroft-Gault equation.
- Hepatic: There should be no evidence of hepatic dysfunction which is defined as a serum bilirubin of \> 1.5 mg/dl and Aspartate Amino Transferase (AST) / Alanine Amino Transferase (ALT) \> 3X the upper limit of normal,
- Hematologic: Absolute neutrophil counts (ANC) \< 1000/mm3 and platelets counts \< 150,000/μL.
- Pulmonary function with a corrected Diffusing Capacity of lung for Carbon Monoxide (DLCO) of \< 50% predicted
- History of a FVIII inhibitor (\>0.6 Bethesda Units/ml) including at least 2 measurements over the preceding 5 years or any single titer \>5 Bethesda Units (BU) /ml.
- Previous stem cell transplant.
- HIV positive.
- Evidence of hepatitis B active infection or chronic carrier
- Evidence of chronic hepatitis C infection. Absence of chronic infection will be documented with at least 2 negative viral loads at least 6 months apart.
- Diagnosis of a bleeding disorder other than hemophilia A
- Use of medication(s) that can affect hemostasis (e.g. aspirin and non- cyclooxygenase (COX-2) selective non-steroid anti-inflammatory drugs).
- History of cancer or familial cancer syndromes
- Any condition in the opinion of the principle investigator that will negatively impact the subject's ability to safely undergo an autologous stem cell transplant.
- Any reason in the opinion of the principle investigator that will negatively impact the subject's ability to complete the clinical trial per the trial protocol.
Key Trial Info
Start Date :
April 1 2022
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
June 28 2024
Estimated Enrollment :
6 Patients enrolled
Trial Details
Trial ID
NCT05265767
Start Date
April 1 2022
End Date
June 28 2024
Last Update
July 12 2024
Active Locations (1)
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1
Christian Medical College Vellore Ranipet Campus
Vellore, Tamil Nadu, India, 632517