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A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Adults and Children With Bone Marrow Failure Syndromes or Inherited Metabolic or Hematologic Diseases


Phase 2
N/A
N/A
Not Enrolling
Both
Graft Versus Host Disease, Leukemia, Myelodysplastic Syndromes, Thymic Carcinoma

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Trial Information

A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Adults and Children With Bone Marrow Failure Syndromes or Inherited Metabolic or Hematologic Diseases


OBJECTIVES: I. Determine the rates of durable engraftment in patients with severe aplastic
anemia, myelodysplastic syndrome, inborn errors of metabolism, or inherited hematopoietic
disorders refractory to medical management, who are undergoing high dose chemoradiotherapy
followed by unrelated cord blood (UCB) transplantation. II. Determine the incidence and
severity of acute and chronic graft-versus-host disease in these patients. III. Monitor
overall and event-free survival of these patients. IV. Evaluate rate and quality of
immunologic reconstitution of these patients. V. Determine whether nucleated cell or
progenitor cell content of the graft is predictive of engraftment.

OUTLINE: This is a multicenter study. Patients are stratified according to low vs high
weight. Patients with severe aplastic anemia, myelodysplastic syndrome, or bone marrow
failure receive cyclophosphamide IV over 1 hour on days -6 to -3 or melphalan IV over 20
minutes on days -4 to -2, antithymocyte globulin (ATG) IV over 4 hours or methylprednisolone
IV over 1 hour twice a day on days -3 to -1, and total lymphoid irradiation on day -1. On
day 0, patients receive umbilical cord blood (UCB) infusion. Patients with inborn errors of
metabolism or inherited hematopoietic disorders receive oral busulfan every 6 hours on days
-9 to -6, cyclophosphamide IV over 1 hour on days -5 to -2 or melphalan IV over 20 minutes
on days -4 to -2, and ATG IV over 4 hours or methylprednisolone IV over 1 hour on days -3 to
-1. On day 0, patients receive UCB infusion. Patients with Fanconi's anemia receive ATG IV
over 4 hours or methylprednisolone IV over 1 hour on days -6 to -1, cyclophosphamide IV over
1 hour on days -5 to -2, thoracoabdominal irradiation on day -1, and then the UCB infusion
on day 0. Patients also receive cyclosporine and methylprednisolone beginning on day -2 and
continuing as necessary as graft-versus-host disease prophylaxis. Patients are followed
indefinitely for survival and late toxicity.

PROJECTED ACCRUAL: A total of 4-90 patients will be accrued for this study within 5 years.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically confirmed diagnosis of one of the following: -
Severe aplastic anemia with bone marrow cellularity less than 20% and at least 2 of the
following criteria: Granulocyte count less than 500/mm3 Platelet count less than
20,000/mm3 Reticulocyte count less than 50,000/mm3 Etiologies may be Fanconi's anemia,
hypoplastic leukemia, monosomy 7, drug exposure (chloramphenicol, NSAIDS), viral exposure
(EBV, hepatitis, parvovirus, HIV), nutritional deficiencies, thymoma, paroxysmal nocturnal
hemoglobinuria, and amegakaryocytic thrombocytopenia - Myelodysplastic syndrome (MDS) that
is refractory to medical management or with cytogenetic abnormalities predictive of
transformation into acute leukemia, including 5q-, 7q-, monosomy 7, and trisomy 8 De novo
primary or therapy-related secondary MDS Refractory anemia or refractory anemia with
ringed sideroblasts only - Inherited hematopoietic disorders that are refractory to
medical management Severe combined immunodeficiency Familial erythrophagocytic
lymphohistiocytosis Wiskott-Aldrich syndrome Kostmann's syndrome (infantile
agranulocytosis) Chronic granulomatous disease Leukocyte adhesion deficiency
Chediak-Higashi syndrome Paroxysmal nocturnal hemoglobinuria Fanconi's anemia Dyskeratosis
congenita Diamond-Blackfan anemia Amegakaryocytic thrombocytopenia Osteopetrosis Gaucher's
disease Lesch-Nyhan syndrome Mucopolysaccharidoses Lipidoses Must also meet all the
following conditions: No HLA-ABC/DR identical related bone marrow or UCB donor No 5/6
antigen matched related bone marrow or UCB donor Condition precludes waiting to search and
find a donor in the National Marrow Donor Registry Must have backup autologous or
haploidentical related marrow Must have available serologic match umbilical cord blood
unit in the New York Blood Center's Placental Blood Project

PATIENT CHARACTERISTICS: Age: Not specified Performance status: Zubrod 0-1 OR Karnofsky or
Lansky 80-100% Life expectancy: At least 3 months Hematopoietic: See Disease
Characteristics Hepatic: Bilirubin no greater than 2.0 mg/dL ALT/AST no greater than 4
times normal Renal: Creatinine no greater than 2.0 mg/dL Creatinine clearance at least 50
mL/min Cardiovascular: Shortening fraction or ejection fraction at least 80% of normal for
age Pulmonary: FVC and FEV1 at least 60% predicted for age Adults: DLCO at least 60%
predicted Other: No active concurrent malignancy No active infections at time of backup
bone marrow harvest or pretransplant cytoreduction Not pregnant or nursing Negative
pregnancy test HIV negative

PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: No concurrent
cytotoxic chemotherapy Endocrine therapy: No concurrent immunosuppressive medications
Radiotherapy: No concurrent radiotherapy Surgery: Not specified

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Barbara Jean Bambach, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Roswell Park Cancer Institute

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000066755

NCT ID:

NCT00003662

Start Date:

August 1998

Completion Date:

January 2001

Related Keywords:

  • Graft Versus Host Disease
  • Leukemia
  • Myelodysplastic Syndromes
  • Thymic Carcinoma
  • noninvasive thymoma and thymic carcinoma
  • recurrent thymoma and thymic carcinoma
  • refractory anemia
  • refractory anemia with ringed sideroblasts
  • de novo myelodysplastic syndromes
  • previously treated myelodysplastic syndromes
  • secondary myelodysplastic syndromes
  • graft versus host disease
  • childhood myelodysplastic syndromes
  • Carcinoma
  • Graft vs Host Disease
  • Hematologic Diseases
  • Leukemia
  • Metabolic Diseases
  • Myelodysplastic Syndromes
  • Preleukemia
  • Thymoma

Name

Location

Roswell Park Cancer InstituteBuffalo, New York  14263
H. Lee Moffitt Cancer Center and Research InstituteTampa, Florida  33612
Rush-Presbyterian-St. Luke's Medical CenterChicago, Illinois  60612
University of Chicago Cancer Research CenterChicago, Illinois  60637
Lineberger Comprehensive Cancer Center, UNCChapel Hill, North Carolina  27599-7295
Duke Comprehensive Cancer CenterDurham, North Carolina  27710
Medical University of South CarolinaCharleston, South Carolina  29425-0721
University of Florida Health Science CenterGainesville, Florida  32610-0296
Hackensack University Medical CenterHackensack, New Jersey  07601
Children's Hospital of New OrleansNew Orleans, Louisiana  70118
Cardinal Glennon Children's HospitalSaint Louis, Missouri  63104
St. Christopher's Hospital for ChildrenPhiladelphia, Pennsylvania  19134-1095
University of South Carolina School of MedicineColumbia, South Carolina  29203
Division of Pediatric SurgeryJacksonville, Florida  32207
New York Blood CenterNew York, New York  10021