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Pilot Study Of Unrelated UCB Transplant for Non-Malignant Hematologic Conditions

This study has been completed.
Sponsor:
Collaborator:
Information provided by:
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT00003336
First received: November 1, 1999
Last updated: June 10, 2010
Last verified: June 2010
  Purpose

RATIONALE: Umbilical cord blood transplantation may allow doctors to give higher doses of chemotherapy or radiation therapy and kill more cancer cells.

PURPOSE: This phase II trial is studying how well umbilical cord blood transplantation works in treating patients with severe aplastic anemia, malignant thymoma, or myelodysplasia.


Condition Intervention Phase
Leukemia
Myelodysplastic Syndromes
Myelodysplastic/Myeloproliferative Diseases
Biological: anti-thymocyte globulin
Drug: busulfan
Drug: cyclophosphamide
Drug: melphalan
Drug: methylprednisolone
Procedure: bone marrow ablation with stem cell support
Procedure: umbilical cord blood transplantation
Radiation: radiation therapy
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Event-free survival by disease assessment [ Time Frame: at 100 days and at 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Umbilical cord blood donor engraftment by chimerism and complete blood count (CBC) at time of myeloid recovery. [ Time Frame: 100 days and at 6, 9, 12, 18, and 24 months ] [ Designated as safety issue: No ]

Enrollment: 6
Study Start Date: January 1998
Study Completion Date: February 2006
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: anti-thymocyte globulin
    The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
    Drug: busulfan
    The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
    Drug: cyclophosphamide
    The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
    Drug: melphalan
    The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
    Drug: methylprednisolone
    The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
    Procedure: bone marrow ablation with stem cell support Procedure: umbilical cord blood transplantation
    One day after the conditioning regimen is completed, patients receive the UCBT.
    Radiation: radiation therapy
    The regimen varies according to the underlying cause of the anemia.Patients receive high-dose chemotherapy and/or radiotherapy as a conditioning regimen beginning 6-9 days before the umbilical cord blood transplant (UCBT).
Detailed Description:

OBJECTIVES:

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

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.

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

  Eligibility

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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/mm^3
    • Platelet count less than 20,000/mm^3
    • Reticulocyte count less than 50,000/mm^3
  • 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

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 FEV_1 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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00003336

Locations
United States, Ohio
Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44106-7284
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Principal Investigator: Mary J. Laughlin, MD Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Responsible Party: Mary J. Laughlin, MD, Ireland Cancer Center at University Hospitals Case Medical Center, Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT00003336     History of Changes
Other Study ID Numbers: CWRU5Y97, P30CA043703, CASE-CWRU-5Y97, NCI-G98-1431, CASE-5Y97
Study First Received: November 1, 1999
Last Updated: June 10, 2010
Health Authority: United States: Federal Government

Keywords provided by Case Comprehensive Cancer Center:
refractory anemia
refractory anemia with ringed sideroblasts
de novo myelodysplastic syndromes
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
atypical chronic myeloid leukemia
myelodysplastic/myeloproliferative disease, unclassifiable
childhood myelodysplastic syndromes

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Myelodysplastic-Myeloproliferative Diseases
Myeloproliferative Disorders
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Antilymphocyte Serum
Cyclophosphamide
Methylprednisolone
Methylprednisolone Hemisuccinate
Methylprednisolone acetate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Alkylating Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antirheumatic Agents
Autonomic Agents

ClinicalTrials.gov processed this record on November 27, 2014