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

NCT ID: NCT00578435

Last Updated: 2008-09-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

1994-01-31

Study Completion Date

2008-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Genetic Disorders Sickle Cell Anemia

Keywords

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ERYTHROPOIESIS Genetic Disorders Sickle Cell Anemia Thalassemia Diamond Blackfan Anemia

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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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

Intervention Type PROCEDURE

Eligibility Criteria

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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
* Severe residual functional neurologic impairment
* Stage III-IV sickle chronic lung disease
* Pregnant or lactating women are excluded
Minimum Eligible Age

1 Year

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Memorial Sloan Kettering Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Memorial Sloan-Kettering Cancer Center

Principal Investigators

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Farid Boulad, MD

Role: PRINCIPAL_INVESTIGATOR

Memorial Sloan Kettering Cancer Center

Locations

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Memorial Sloan-Kettering Cancer Center

New York, New York, United States

Site Status

Countries

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United States

Related Links

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http://www.mskcc.org

Memorial Sloan-Kettering web site

Other Identifiers

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94-005

Identifier Type: -

Identifier Source: org_study_id