Allogeneic Bone Marrow Transplantation for the Treatment of Genetic Disorders of Erythropoiesis

Sickle Cell Anemia Clinical Trial

Official title:

Allogeneic Bone Marrow Transplantation for the Treatment of Genetic Disorders of Erythropoiesis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00578435
• Other study ID #: 94-005
• Status: Completed
• Phase: Phase 2
• First received: December 18, 2007
• Last updated: September 10, 2008
• Start date: January 1994
• Est. completion date: August 2008

Study information

• Verified date: September 2008
• Source: Memorial Sloan Kettering Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine and confirm the role of bone marrow transplantation in the treatment of disorders of the red cell and hemoglobin including sickle cell anemia, thalassemia and diamond blackfan anemia.

Description:

The trial proposed is a single armed phase II treatment protocol designed to examine the engraftment,toxicity and graft-versus-host disease following a novel cytoreductive regimen including cyclophosphamide and Busulfan for the treatment of patients with Severe Sickle Cell Anemia,Thalassemia, and Diamond Blackfan Anemia using stem cell transplants derived from HLA-genotypically identical siblings.

Patients will be conditioned for transplantation with cyclophosphamide (50 mg/kg/day x 4 days), and busulfan [(if < 4 years of age 1 mg/kg 4 times per day x 4 days), (if > 4 years of age 0.8 mg/kg 4 times per day x 4 days)]. Patients will receive Methotrexate & Cyclosporin-A for prophylaxis against GvHD and GCSF to promote engraftment.

The preferred source of stem cells from related HLA-matched related donors will be unmodified bone marrow stem cells.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: August 2008
• Est. primary completion date: August 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 1 Year and older

Eligibility

Inclusion Criteria:

• Patients with severe HOMOZYGOUS SICKLE CELL ANEMIA or SICKLE/BETA THALASSEMIA

• Neurologic event (stroke or hemorrhage).

• Abnormal cerebral MRI scan and cerebral arteriogram or MRI angiographic study (MRA) and impaired neuropsychologic testing.

• Recurrent acute chest syndrome (> 2 episodes)

• Stage I-II sickle chronic lung disease

• Sickle cell nephropathy (moderate or severe proteinuria or GFR 30-50% of predicted for age.

• Major visual impairment in at least one eye with bilateral proliferative retinopathy.

• Osteonecrosis of multiple bones

• Chronic debilitating pain secondary to vasoocclusive crisis (>= 3 episodes per year for >= 3 years) Recurrent priapism

• Allo-immunization with the development of antibodies following chronic transfusion therapy

• Patients with HOMOZYGOUS SICKLE CELL ANEMIA or SICKLE/BETA THALASSEMIA with the following criteria will be considered for accrual on this protocol

• Patients < 2 years with high WBC counts and/or >1 episode of dactylitis and/or a Hgb < 7 g/dl

• History of death from sickle cell disease in sibship of patient

• Patients with BETA-THALASSEMIA MAJOR with Lucarelli class 1 or 2 risk status i.e with only 0-2 of the following factors: hepatomegaly, portal fibrosis, or poor chelation therapy

• Patients with DIAMOND-BLACKFAN ANEMIA who have failed conventional therapy.

• Patients must have an HLA-compatible related donor. The donor must be healthy and able to undergo general anesthesia. Donors with heterozygous sickle cell anemia (hemoglobin AS) or with heterozygous thalassemia are acceptable donors.

• At the time of referral for transplantation, patients must be in good clinical condition without any evidence of infections and a Karnofsky or Lansky pediatric performance scale > 70%

• Each patient and donor must be willing to participate as a research subject and must sign an informed consent form after having been advised as to the nature and risk of the study prior to entering the protocol. Parents or legal guardians of patients who are minor will sign the consent form after being advised of the nature and risks of the study

Exclusion Criteria:

• Patients whose life expectancy is less than 8 weeks. Patients with a Karnofsky or Lansky performance score of < 70%

• Patients with severe major organ dysfunction:

• Patients with severe renal impairment. This will be determined by a creatinine clearance < 70 ml/min/1.73 m2 (or serum creatinine > 1.5 x Normal) or by a glomerular filtration rate < 30% of predicted normal for age

• Inadequate cardiac function as determined by fractional shortening < 28% on echocardiogram, and/or ejection fraction of < 50% on echocardiogram or RNCA.

• Patients with FS of 23-28% who show an increase in FS in response to stress on the supine bicycle ergometer are eligible

• Major liver dysfunction: SGOT > 3 x upper limit of normal. Hyperbilirubinemia will not be used as an exclusion criteria because of the hemolytic component of the bilirubin. Patients with active hepatitis or severe liver fibrosis will also be excluded

• Severe residual functional neurologic impairment

• Stage III-IV sickle chronic lung disease

• Pregnant or lactating women are excluded

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Genetic Diseases, Inborn
• Genetic Disorders
• Sickle Cell Anemia

Intervention

Procedure:
• Busulfan, Cyclophosphamide, BMD
Busulfan 0.8 or 1 mg/Kg/day Days 8-6 Cyclophosphamide 50 mg/Kg/day Days 2-5 BMT Day 0

Locations

Country	Name	City	State
United States	Memorial Sloan-Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Define the role of bone marrow transplantation for the treatment of sickle cell disease and the reversibility of sickle cell vasculopathy and organ damage, good risk thalassemia major and Diamond-Blackfan Anemia.		2 years	Yes

External Links

•   Memorial Sloan-Kettering web site