Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Umbilical Cord Blood Transplantation in Treating Patients With Severe Aplastic Anemia, Malignant Thymoma, or Myelodysplasia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	55 and under	NCI	CASE-CWRU-5Y97 NCI-G98-1431, NCT00003336, CASE-5Y97

Objectives

1. 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.
2. Evaluate the rate and quality of immunologic reconstitution in this patient population.

Entry Criteria

Disease Characteristics:

• Histologically confirmed diagnosis of severe aplastic anemia based on bone marrow cellularity of less than 20%



• Must meet at least two of the following criteria:
  • Granulocyte count less than 500/mm³
  • Platelet count less than 20,000/mm³
  • Reticulocyte count less than 50,000/mm³



• Following etiologies eligible:
  • Fanconi's anemia
  • Hypoplastic leukemia
  • Monosomy 7
  • Drug exposure (chloramphenicol, NSAIDS)
  • Viral exposure (EBV, hepatitis, parvovirus, HIV)
  • Nutritional deficiencies
  • Thymoma
  • Paroxysmal nocturnal hemoglobinuria
  • Amegakaryocytic thrombocytopenia

  OR

• Histologically confirmed myelodysplastic syndrome (MDS) that is refractory to medical management or with cytogenic abnormalities predictive of transformation into acute leukemia, including 5q-, 7q-, monosomy 7, or trisomy 8



• The following etiologies only are eligible:
  • Refractory anemia
  • Refractory anemia with ringed sideroblasts
  • De novo primary MDS
  • Therapy-related secondary MDS

  OR

• Confirmed diagnosis of inherited hematopoietic disorder that is refractory to medical management



• Following etiologies eligible:
  • Severe combined immunodeficiency
  • Familial erythrophagocytic lymphohistiocytosis
  • Wiskott-Aldrich syndrome
  • Kostmann's syndrome (infantile histiocytosis)
  • Chronic granulomatous disease
  • Leukocytic 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
  • Lipodoses

• Autologous or haploidentical related peripheral blood stem cells available as backup



• Serologically matched umbilical cord blood unit available in the New York Blood Center's Placental Blood Project, or other acceptable umbilical cord blood registry

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

Patient Characteristics:

Age:

• 55 and under

Performance status:

• Zubrod 0-1
• Karnofsky 80-100%

Life expectancy:

• At least 3 months

Hematopoietic:

• See Disease Characteristics

Hepatic:

• ALT/AST no greater than 4 times normal
• Bilirubin no greater than 2.0 mg/dL

Renal:

• Creatinine no greater than 2.0 mg/dL
• Creatinine clearance at least 50 mL/min

Cardiovascular:

• Normal cardiac function by echocardiogram or radionuclide scan
• Shortening fraction or ejection fraction at least 80% normal for age
• Non-Fanconi patients with acquired or congenital cardiomyopathy may receive melphalan as a substitute for cyclophosphamide

Pulmonary:

• FVC and FEV₁ at least 60% of predicted for age
• DLCO at least 60% of predicted in adult patients

Other:

• No active concurrent malignancy
• No active infection
• Not pregnant or nursing
• HIV negative
• Must have an available serologic matched Umbilical Cord Blood Unit (UCBU) in the New York Blood Center's Placental Blood Project, or other acceptable Umbilical Cord Blood (UCB) registry

Expected Enrollment

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

Outcomes

Event-free survival by disease assessment at 100 days and at 6, 9, 12, 18, and 24 months

Umbilical cord blood donor engraftment by chimerism and complete blood count (CBC) at time of myeloid recovery, 100 days and at 6, 9, 12, 18, and 24 months

Outline

Patients are stratified according to weight (under 45 kg vs over 45 kg).

Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT). The regimen varies according to the underlying cause of the anemia, but could include busulfan, cyclophosphamide or melphalan, anti-thymocyte globulin or methylprednisolone, and/or radiation therapy. One day after the conditioning regimen is completed, patients receive the UCBT.

Patients are followed weekly for 3 months, at 6 months, then every 6 months for 2.5 years, then annually thereafter.

Laughlin MJ, Barker J, Bambach B, et al.: Hematopoietic engraftment and survival in adult recipients of umbilical-cord blood from unrelated donors. N Engl J Med 344 (24): 1815-22, 2001.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Case Comprehensive Cancer Center

Mary Laughlin, MD, Protocol chair		Ph: 216-368-5693 Email: mjl13@po.cwru.edu

Registry Information
Official Title		A Pilot Study of Unrelated Umbilical Cord Blood Transplantation in Patients with Severe Aplastic Anemia, Inborn Errors in Metabolism, or Inherited Hematologic Stem Cell Disorders
Trial Start Date		1998-01-06
Registered in ClinicalTrials.gov		NCT00003336
Date Submitted to PDQ		1998-05-19
Information Last Verified		2006-04-01
NCI Grant/Contract Number		CA43703

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