Stem Cell Transplant for Hemoglobinopathy

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT00176852
• Date of registration: 12/09/2005
• Prospective Registration: No
• Primary sponsor: Masonic Cancer Center, University of Minnesota
• Public title: Stem Cell Transplant for Hemoglobinopathy
• Scientific title: Allogeneic Hematopoietic Stem Cell Transplant for Patients With High Risk Hemoglobinopathy Using a Preparative Regimen to Achieve Stable Mixed Chimerism
• Date of first enrolment: June 2002
• Target sample size: 22
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00176852
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2/Phase 3

Countries of recruitment

United States

Contacts

• Name: Angela Smith, MD
• Affiliation: Masonic Cancer Center, University of Minnesota

Key inclusion & exclusion criteria

Inclusion Criteria:

- Patients with Sickle Cell Disease/Thalassemia (SCD/THAL) 0-50 years of age with an
acceptable stem cell donor and disease characteristic defined by the following:

- Stroke, central nervous system (CNS) hemorrhage or a neurologic event lasting
longer than 24 hours, or abnormal cerebral magnetic resonance imaging (MRI) or
cerebral arteriogram or MRI angiographic study and impaired neuropsychological
testing

- Acute chest syndrome with a history of recurrent hospitalizations or exchange
transfusions

- Recurrent vaso-occlusive pain 3 or more episodes per year for 3 years or more
years or recurrent priapism,

- Impaired neuropsychological function and abnormal cerebral MRI scan

- Stage I or II sickle lung disease,

- Sickle nephropathy (moderate or severe proteinuria or a glomerular filtration
rate [GFR] 30-50% of the predicted normal value)

- Bilateral proliferative retinopathy and major visual impairment in at least one
eye

- Osteonecrosis of multiple joints with documented destructive changes

- Requirement for chronic transfusions but with red blood cell (RBC)
alloimmunization >2 antibodies during long term transfusion therapy

- Patients with transfusion dependent alpha- or beta-thalassemia 0-35 years of age with
an acceptable stem cell donor as defined in the criteria in section above.

- Patients with other non-malignant hematologic disorders that are transfusion-dependent
or involve other potentially life-threatening cytopenias (including but not limited to
Severe Congenital Neutropenia, Diamond-Blackfan Anemia and Shwachman-Diamond Syndrome)
who are 0-35 years of age with an acceptable stem cell donor

- Second Transplants

- Patients with sickle cell disease or thalassemia who have failed to engraft or
have autologous recovery after a myeloablative SCT regimen or non-myeloablative
regimen are eligible for this protocol.

- Regimen A2 will be utilized for patients with sickle cell disease or thalassemia
who do not have an HLA-identical sibling donor or for any patient who has
pre-existing organ dysfunction making them ineligible for a myeloablative
preparative regimen.

- Regimen B will be utilized for patients with sickle cell disease or thalassemia
who have an HLA-identical sibling donor.

- Patients must meet above criteria.

- If the patient has received prior radiation therapy, eligibility to receive
additional radiation therapy must be determined by Dr. Dusenbery

- If first transplant was a non-myeloablative regimen, the second transplant can
occur at any time

- If the first transplant was a myeloablative regimen, then the second transplant
must be > 6 months from the first transplant

Exclusion Criteria:

- Patients with one or more of the following:

- Karnofsky or Lansky performance score <70

- Acute hepatitis or evidence of moderate or severe portal fibrosis or cirrhosis on
biopsy

- Stage III-IV lung disease

- GFR<30% predicted

- Pregnant or lactating females

- Active serious infection whereby patient has been on intravenous antibiotics for one
week prior to study entry. Any patient with AIDS or ARC or HIV seropositivity

- Psychologically incapable of undergoing bone marrow transplant (BMT) with associated
strict isolation or documented history of medical non-compliance

- Patients not able to receive total lymphocytic irradiation (TLI) due to prior
radiation therapy



Age minimum: N/A
Age maximum: 50 Years
Gender: All

Health Condition(s) or Problem(s) studied

Diamond-Blackfan Anemia

Shwachman-Diamond Syndrome

Sickle Cell Disease

Thalassemia

Severe Congenital Neutropenia

Intervention(s)

Drug: Campath, Fludarabine, Cyclophosphamide

Drug: Busulfan, Fludarabine, ATG, TLI

Drug: Busulfan, Cyclophosphamide, ATG, GCSF

Procedure: Stem cell infusion

Radiation: Total Body Irradiation

Primary Outcome(s)

Number of Patients Who Experienced Grade 3-5 Treatment Related Toxicity [Time Frame: 1 year]

Secondary Outcome(s)

Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment [Time Frame: pre-transplant]

The Incidence of Grade 2-4 Acute Graft Versus Host Disease (Acute GVHD) [Time Frame: 100 days]

The Incidence of Chimerism at 100 Days [Time Frame: 100 days]

Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment [Time Frame: 2 years]

Disease Free Survival [Time Frame: 1 year]

Determine Physical Characteristics and Biologic Effects of Mixed Populations of Donor and Host Red Blood Cells [Time Frame: During study]

Change in the Patient's Quality of Life as Compared to the Pre-Transplant Assessment [Time Frame: 1 year]

The Incidence of Chimerism at 6 Months [Time Frame: 6 months]

Determine the Concentration of Campath in the Serum [Time Frame: Day 0]

The Incidence of Chimerism at 1 Year [Time Frame: 1 year]

The Incidence of Chronic Graft Versus Host Disease (Chronic GVHD) [Time Frame: 6 months]

The Incidence of Grade 3-4 Acute Graft Versus Host Disease (Acute GVHD) [Time Frame: 100 days]

Disease Free Survival [Time Frame: 100 days]

Overall Survival [Time Frame: 1 year]

The Incidence of Chronic Graft Versus Host Disease (Chronic GVHD) [Time Frame: 1 year]

Overall Survival [Time Frame: 100 days]

Secondary ID(s)

0206M26241

MT2002-07

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Marrow Donor Program

Results

• Results available: Yes
• Date Posted: 09/05/2017
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00176852