Umbilical Cord Blood for Stem Cell Transplantation in Treating Young Patients With Malignant or Nonmalignant Diseases - Full Text View

Sponsored by:	Milton S. Hershey Medical Center
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00084695

Purpose

RATIONALE: Umbilical cord blood transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy.

PURPOSE: This phase II trial is studying how well umbilical cord blood works as a source of stem cells in treating patients with types of cancer as well as other diseases.

Condition	Intervention	Phase
Fanconi Anemia Langerhans Cell Histiocytosis Leukemia Lymphoma Myelodysplastic Syndromes Neuroblastoma Sarcoma Unspecified Childhood Solid Tumor, Protocol Specific	Drug: anti-thymocyte globulin Drug: busulfan Drug: cyclophosphamide Drug: fludarabine phosphate Drug: melphalan Drug: methylprednisolone Procedure: radiation therapy	Phase II

MedlinePlus related topics: Anemia Cancer Hodgkin's Disease Leukemia, Adult Acute Leukemia, Adult Chronic Leukemia, Childhood Lymphoma Neuroblastoma Soft Tissue Sarcoma

Drug Information available for: Cyclophosphamide Methylprednisolone Melphalan Fludarabine Fludarabine monophosphate Melphalan hydrochloride Sarcolysin Busulfan

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label
Official Title:	The Use Of Umbilical Cord Blood As A Source Of Hematopoietic Stem Cells

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:

Impact of the use of umbilical cord blood as a source of hematopoietic stem cells [ Designated as safety issue: No ]
Comparison of the incidence of graft-vs-host disease with historical data [ Designated as safety issue: No ]
Comparison of the incidence of engraftment with historical data [ Designated as safety issue: No ]

Estimated Enrollment:	25
Study Start Date:	September 2003
Estimated Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Regimen A: Experimental Patients undergo total body irradiation (TBI) two times daily on days -7 to -4. Patients receive cyclophosphamide IV over 30-60 minutes on days -3 and -2 and anti-thymocyte globulin (ATG) IV over at least 6 hours on days -3 to -1.	Drug: anti-thymocyte globulin Given IV Drug: cyclophosphamide Given IV Procedure: radiation therapy Patients undergo radiation therapy two times daily on days -7 to -4.
Regimen B (patients who do not receive TBI): Experimental Patients receive oral busulfan 4 times daily on days -8 to -5, and ATG IV over at least 6 hours and melphalan IV over 15-20 minutes on days -4 to -2.	Drug: anti-thymocyte globulin Given IV Drug: busulfan Given orally Drug: melphalan Given IV
Regimen C (patients with Fanconi's anemia/related disorders): Experimental Patients undergo TBI on day -6. Patients receive ATG IV over at least 6 hours and methylprednisolone IV on days -5 to -1 and fludarabine IV over 30 minutes and cyclophosphamide IV over 30-60 minutes on days -5 to -2.	Drug: anti-thymocyte globulin Given IV Drug: cyclophosphamide Given IV Drug: fludarabine phosphate Given IV Drug: methylprednisolone Given IV Procedure: radiation therapy Patients undergo radiation therapy two times daily on days -7 to -4.
Regimen D: Experimental Patients receive oral or IV busulfan 4 times daily on days -9 to -5, ATG IV over at least 6 hours on days -5 to -3, and cyclophosphamide IV over 30-60 minutes on days -5 to -2.	Drug: anti-thymocyte globulin Given IV Drug: busulfan Given orally Drug: cyclophosphamide Given IV

Detailed Description:

OBJECTIVES:

Primary

Determine the impact of the use of umbilical cord blood as a source of hematopoietic stem cells for children with life-threatening oncologic, hematologic, or genetic/metabolic disorders in need of a stem cell transplant.
Compare the incidence of graft-versus-host disease in patients receiving cord blood transplants in this study with historical data for unrelated donor stem cell transplants.
Compare the incidence of engraftment in patients receiving cord blood transplants in this study with historical data for unrelated donor stem cell transplants.

OUTLINE:

Preparative therapy: Patients are treated on 1 of 4 preparative therapy regimens.
- Regimen A: Patients undergo total body irradiation (TBI) two times daily on days -7 to -4. Patients receive cyclophosphamide IV over 30-60 minutes on days -3 and -2 and anti-thymocyte globulin (ATG) IV over at least 6 hours on days -3 to -1.
- Regimen B (patients who do not receive TBI): Patients receive oral busulfan 4 times daily on days -8 to -5, and ATG IV over at least 6 hours and melphalan IV over 15-20 minutes on days -4 to -2.
- Regimen C (patients with Fanconi's anemia and related disorders): Patients undergo TBI on day -6. Patients receive ATG IV over at least 6 hours and methylprednisolone IV on days -5 to -1 and fludarabine IV over 30 minutes and cyclophosphamide IV over 30-60 minutes on days -5 to -2.
- Regimen D: Patients receive oral or IV busulfan 4 times daily on days -9 to -5, ATG IV over at least 6 hours on days -5 to -3, and cyclophosphamide IV over 30-60 minutes on days -5 to -2.
Cord blood transplant: All patients undergo umbilical cord blood transplantation on day 0.
Graft-versus-host disease prophylaxis: Patients receive oral or IV cyclosporine twice daily beginning on day -1. Patients also receive methylprednisolone IV twice daily beginning on day 5 and continuing until at least day 28.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	up to 21 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of malignant or non-malignant disease, including but not limited to any of the following:
- Acute myeloid leukemia or acute lymphoblastic leukemia (ALL) with resistant disease beyond first clinical remission (CR)
- ALL in first CR at high-risk because of 1 of the following factors:
  - Hypoploidy
  - Pseudodiploidy with translocations t(9;22), t(4;11), or t(8;14)
  - Elevated WBC at diagnosis as follows:
    - > 100,000/mm^3 for patients 6-12 months of age
    - > 50,000/mm^3 for patients 10-20 years of age
    - > 20,000/mm^3 for patients 21 years of age
  - Burkitt's lymphoma/leukemia
- Chronic myelogenous leukemia in first chronic phase or beyond
- Juvenile myelomonocytic leukemia
- Advanced stage or relapsed lymphoma
- Advanced stage or relapsed solid tumors, including any of the following:
  - Neuroblastoma
  - Ewing's sarcoma
  - Rhabdomyosarcoma
- Myelodysplastic syndromes, excluding patients with grade 3 or 4 myelofibrosis
- Familial erythrophagocytic histiocytosis
- Histiocytosis unresponsive to medical management
- Inborn errors of metabolism
- Langerhans cell histiocytosis unresponsive to medical management
- Immune deficiencies, including:
  - Severe combined immune deficiency
  - Wiskott-Aldrich
- Hemoglobinopathies, including sickle cell disease and thalassemia
- Severe aplastic anemia
- Fanconi's anemia
- Metabolic storage diseases
Unrelated cord blood donor must be HLA-identical OR may be mismatched for 1, 2, or 3 HLA-loci (A, B, DR)
No other existing HLA-identical related donor available at the time of transplantation

PATIENT CHARACTERISTICS:

Age

21 and under

Performance status

Not specified

Life expectancy

Not specified

Hematopoietic

See Disease Characteristics

Hepatic

Not specified

Renal

Not specified

PRIOR CONCURRENT THERAPY:

Biologic therapy

Not specified

Chemotherapy

Not specified

Endocrine therapy

Not specified

Radiotherapy

Not specified

Surgery

Not specified

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00084695

Locations

United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center	Recruiting
Hershey, Pennsylvania, United States, 17033-0850
Contact: Kenneth G. Lucas, MD 717-531-6012 klucas@psu.edu

Sponsors and Collaborators

Milton S. Hershey Medical Center

Investigators

Study Chair:

Kenneth G. Lucas, MD

Penn State Children's Hospital

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Responsible Party:	Penn State Children's Hospital ( Kenneth Gerald Lucas )
Study ID Numbers:	CDR0000365544, PSCI-2003-232
Study First Received:	June 10, 2004
Last Updated:	October 28, 2008
ClinicalTrials.gov Identifier:	NCT00084695
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

childhood myelodysplastic syndromes
recurrent childhood rhabdomyosarcoma
unspecified childhood solid tumor, protocol specific
previously treated childhood rhabdomyosarcoma
previously untreated childhood rhabdomyosarcoma
disseminated neuroblastoma
regional neuroblastoma
recurrent neuroblastoma
metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
recurrent childhood acute lymphoblastic leukemia
juvenile myelomonocytic leukemia
childhood acute lymphoblastic leukemia in remission
Burkitt lymphoma
recurrent childhood lymphoblastic lymphoma

stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
recurrent childhood small noncleaved cell lymphoma
stage III childhood small noncleaved cell lymphoma
stage IV childhood small noncleaved cell lymphoma
recurrent childhood large cell lymphoma
stage III childhood large cell lymphoma
stage IV childhood large cell lymphoma
stage III childhood Hodgkin lymphoma
stage IV childhood Hodgkin lymphoma
previously treated myelodysplastic syndromes
Fanconi anemia
de novo myelodysplastic syndromes
secondary myelodysplastic syndromes
childhood chronic myelogenous leukemia

Study placed in the following topic categories:

Juvenile myelomonocytic leukemia
Neuroectodermal Tumors, Primitive
Chronic myelogenous leukemia
Methylprednisolone
Malignant mesenchymal tumor
Langerhans cell histiocytosis
Small non-cleaved cell lymphoma
Neoplasms, Connective and Soft Tissue
Letterer-Siwe disease
Ewing's sarcoma
Preleukemia
Neoplasm Metastasis
Neuroepithelioma
Hodgkin Disease
Methylprednisolone Hemisuccinate

Rhabdomyosarcoma
Myelodysplastic syndromes
Lymphoma, Large B-Cell, Diffuse
Lung Diseases, Interstitial
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Metabolic Diseases
Immunoproliferative Disorders
Hematologic Diseases
Acute myelogenous leukemia
Leukemia, Myeloid
Neuroectodermal Tumors
Hodgkin lymphoma, childhood
Lung Diseases
Sarcoma
Fludarabine

Additional relevant MeSH terms:

Antimetabolites
Anti-Inflammatory Agents
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Neoplasms, Nerve Tissue
DNA Repair-Deficiency Disorders
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Antiemetics
Hormones
Neuroprotective Agents
Pathologic Processes
Syndrome

Therapeutic Uses
Alkylating Agents
Disease
Neoplasms by Histologic Type
Reticuloendotheliosis
Antineoplastic Agents, Hormonal
Immune System Diseases
Gastrointestinal Agents
Glucocorticoids
Protective Agents
Immunosuppressive Agents
Pharmacologic Actions
Neoplasms
Anemia, Hypoplastic, Congenital
Autonomic Agents

ClinicalTrials.gov processed this record on January 16, 2009