Know Cancer

forgot password

Evaluation of Fludarabine, Busulfan and Alemtuzumab as a Reduced Toxicity Ablative Bone Marrow Stem Cell Transplant Regimen for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myelodysplastic Syndrome (MDS)/Leukemia

Phase 2
21 Years
Not Enrolling
Congenital Amegakaryocytic Thrombocytopenia, Diamond-blackfan Anemia, Leukemia, Myelodysplastic Syndromes, Severe Congenital Neutropenia

Thank you

Trial Information

Evaluation of Fludarabine, Busulfan and Alemtuzumab as a Reduced Toxicity Ablative Bone Marrow Stem Cell Transplant Regimen for Children With Stem Cell Defects, Marrow Failure Syndromes, or Myelodysplastic Syndrome (MDS)/Leukemia



- 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.


- 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.

Inclusion Criteria


- 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 immunoglobulin M (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 human leukocyte antigen (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+ (Cluster of
differentiation 34-positive) cells per kg body weight of recipient
available at the time of cryopreservation


- Cardiac ejection fraction ≥ 27%

- Creatinine clearance ≥ 50 mL/min by 24-hour urine collection or glomerular filtration

- DLCO (diffusion capacity of lung for carbon monoxide) ≥ 50% of predicted (corrected
for anemia/lung volume)


- No prior transplantation for leukemia from which patient remains engrafted and
alemtuzumab is not needed as part of the conditioning regimen

Type of Study:


Study Design:

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

Outcome Measure:

Number of Participants Achieving Durable Engraftment (Presence of Donor Cells) at 6 Weeks Post Transplantation

Outcome Description:

Peripheral blood chimerism studies were performed by quantitative real time polymerase chain reaction (qPCR) evaluation of differential short tandem repeat DNA sequences

Outcome Time Frame:

6 weeks post-transplant

Safety Issue:


Principal Investigator

Morton J. Cowan, MD

Investigator Role:

Study Chair

Investigator Affiliation:

University of California, San Francisco


United States: UCSF Cancer Research Center protocol Review Committee

Study ID:




Start Date:

January 2005

Completion Date:

September 2011

Related Keywords:

  • Congenital Amegakaryocytic Thrombocytopenia
  • Diamond-Blackfan Anemia
  • Leukemia
  • Myelodysplastic Syndromes
  • Severe Congenital Neutropenia
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • childhood acute myeloid leukemia in remission
  • childhood chronic myelogenous leukemia
  • congenital amegakaryocytic thrombocytopenia
  • Diamond-Blackfan anemia
  • severe congenital neutropenia
  • secondary acute myeloid leukemia
  • chronic phase chronic myelogenous leukemia
  • childhood myelodysplastic syndromes
  • Anemia
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia
  • Neutropenia
  • Thrombocytopenia
  • Anemia, Diamond-Blackfan



University of Wisconsin Paul P. Carbone Comprehensive Cancer Center Madison, Wisconsin  53792-6164
UCSF Helen Diller Family Comprehensive Cancer Center San Francisco, California  94115