| City: |
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Madison |
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State:
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WI |
| Zip Code: |
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53792 |
| Conditions: |
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Congenital Amegakaryocytic Thrombocytopenia - Diamond-Blackfan Anemia - Leukemia - Myelodysplastic Syndromes - Severe Congenital Neutropenia |
| Purpose: |
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RATIONALE: Monoclonal antibodies, such as alemtuzumab, can block cancer growth in different
ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells
and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy,
such as fludarabine and busulfan, work in different ways to stop the growth of cancer cells,
either by killing the cells or by stopping them from dividing. A peripheral stem cell, bone
marrow , or umbilical cord blood transplant may be able to replace blood-forming cells that
were destroyed by chemotherapy. Sometimes the transplanted cells from a donor can make an
immune response against the body's normal cells. Giving cyclosporine together with
methotrexate and methylprednisolone may stop this from happening.
PURPOSE: This phase II trial is studying how well giving alemtuzumab together with
fludarabine and busulfan works when given before donor stem cell transplant in treating
young patients with hematologic disorders.
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| Study summary: |
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OBJECTIVES:
Primary
- Determine the engraftment rate with reduced toxicity ablative conditioning regimen
comprising alemtuzumab, fludarabine, and busulfan followed by allogeneic stem cell
transplantation in pediatric patients with stem cell defects, marrow failure syndromes,
hemoglobinopathy, severe immunodeficiency syndromes (nonsevere combined
immunodeficiency disorders), myelodysplastic syndromes, or myeloid leukemia.
Secondary
- Determine the acute reactions, incidence of infections, and rate of immune
reconstitution in patients treated with this regimen.
OUTLINE: This is a multicenter study.
- Conditioning regimen: Patients receive alemtuzumab IV over 6 hours on days -12 to -10,
high-dose busulfan IV over 2 hours 4 times daily on days -9 to -6, and fludarabine IV
over 30 minutes on days -5 to -2.
- Allogeneic stem cell transplantation: Two days after the completion of conditioning
regimen, patients undergo allogeneic bone marrow, peripheral blood stem cell, or
umbilical cord blood transplantation on day 0. Patients receive filgrastim (G-CSF)
subcutaneously beginning on day 5 and continuing until blood counts recover.
- Graft-vs-host disease (GVHD) prophylaxis:
- Most transplantations (bone marrow or peripheral blood stem cell transplantation):
Patients receive cyclosporine IV continuously beginning on day -1 until at least
day 50 followed by a taper at either 2 months, 9 months, or 1 year in the absence
of GVHD. Patients also receive methotrexate on days 1, 3, and 6.
- Umbilical cord blood transplantation: Patients receive cyclosporine as in most
transplantations, and methylprednisolone IV twice daily on days 0-21 followed by a
weekly taper.
After transplantation, patients are followed periodically for up to 20 years.
PROJECTED ACCRUAL: A total of 35 patients will be accrued for this study. |
| Criteria: |
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DISEASE CHARACTERISTICS:
- Diagnosis of 1 of the following hematologic conditions:
- Aplastic anemia with marrow aplasia, meeting all of the following criteria:
- Absolute neutrophil count < 500/mm^3
- Platelet and/or red cell transfusion dependent
- Chronic aplastic anemia, meeting all of the following criteria:
- Transfusion dependent
- Unresponsive to immunosuppressive therapy
- Alternative matched unrelated donor has been identified
- Congenital marrow failure syndrome, including any of the following (with closely
matched related or unrelated donor):
- Primary red cell aplasia (Diamond-Blackfan syndrome)
- Congenital neutropenia (Kostmann's syndrome)
- Amegakaryocytic thrombocytopenia
- Congenital dyserythropoietic anemias
- Other severe acquired cytopenias in which a transplantation using a
combined busulfan/cyclophosphamide conditioning regimen is indicated
- Hemoglobinopathy (with closely matched related or unrelated donor)
- β-thalassemia major
- Sickle cell anemia
- Hemoglobin E/β-thalassemia
- Severe immunodeficiency disease
- Chediak-Higashi disease
- Wiskott-Aldrich syndrome
- Combined immunodeficiency disease (Nezelof's)
- Hyper IgM syndrome
- Bare lymphocyte syndrome
- Chronic granulomatous disease
- Familial erythrohemophagocytic lymphohistiocytosis
- Other stem cell defects (e.g., osteopetrosis)
- Severe immune dysregulation/autoimmune disorders
- Achieved a transient response to prior immunosuppressive therapy
- Chronic myelogenous leukemia
- Disease in first chronic phase
- Acute myeloid leukemia
- Disease in first remission
- Myelodysplastic syndromes
- Inborn errors of metabolism
- Histiocytosis
- No severe combined immunodeficiency disease
- Matched related or unrelated donor available by high resolution DNA typing
- Related donor, meeting both of the following criteria:
- Matched at both HLA-Drβ1 alleles
- No more than 1 mismatch at the 4 HLA-A and -B alleles
- Unrelated donor, meeting 1 of the following criteria:
- Marrow matched at both HLA-Drβ1 alleles AND no more than 1 mismatch at the
4 HLA-A and -B alleles
- Umbilical cord blood matched at 5/6 HLA-A, -B, and -DRβ1 alleles with at
least 1 -DRβ1 match AND there are ≥ 3x10^5 CD34+ cells per kg body weight
of recipient available at the time of cryopreservation
PATIENT CHARACTERISTICS:
- Cardiac ejection fraction ≥ 27%
- Creatinine clearance ≥ 50 mL/min by 24-hour urine collection or glomerular filtration
rate
- DLCO ≥ 50% of predicted (corrected for anemia/lung volume)
PRIOR CONCURRENT THERAPY:
- No prior transplantation for leukemia from which patient remains engrafted and
alemtuzumab is not needed as part of the conditioning regimen |
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| Study is available at: |
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University of Wisconsin Paul P. Carbone Comprehensive Cancer Center
Madison, WI 53792
United States
Primary Contact:
Clinical Trials Office - University of Wisconsin Paul P. Carbo
Phone: 608-262-5223 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 21, 2011 |
Modifications to
this listing: |
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above to view all information about this clinical trial. |
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