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

The Use Of Umbilical Cord Blood As A Source Of Hematopoietic Stem Cells

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.

Study Overview

• Status: Unknown
• Conditions: Sarcoma; Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific; Myelodysplastic Syndromes; Leukemia; Fanconi Anemia; Neuroblastoma; Childhood Langerhans Cell Histiocytosis
• Intervention / Treatment: Drug: fludarabine phosphate; Drug: busulfan; Drug: cyclophosphamide; Drug: melphalan; Drug: methylprednisolone; Biological: anti-thymocyte globulin; Radiation: radiation therapy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 21 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: cyclophosphamide; Given IV; Biological: anti-thymocyte globulin; Given IV; Radiation: radiation therapy; Patients undergo radiation therapy two times daily on days -7 to -4.
Experimental: 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.	Drug: busulfan; Given orally; Drug: melphalan; Given IV; Biological: anti-thymocyte globulin; Given IV
Experimental: Regimen C (patients with Fanconi's anemia/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.	Drug: fludarabine phosphate; Given IV; Drug: cyclophosphamide; Given IV; Drug: methylprednisolone; Given IV; Biological: anti-thymocyte globulin; Given IV; Radiation: radiation therapy; Patients undergo radiation therapy two times daily on days -7 to -4.
Experimental: 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.	Drug: busulfan; Given orally; Drug: cyclophosphamide; Given IV; Biological: anti-thymocyte globulin; Given IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Impact of the use of umbilical cord blood as a source of hematopoietic stem cells
Comparison of the incidence of graft-vs-host disease with historical data
Comparison of the incidence of engraftment with historical data

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center
• Investigators: Study Chair: Kenneth G. Lucas, MD, Milton S. Hershey Medical Center

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: June 10, 2004
• First Submitted That Met QC Criteria: June 10, 2004
• First Posted (Estimate): June 11, 2004

Study Record Updates

• Last Update Posted (Estimate): January 10, 2014
• Last Update Submitted That Met QC Criteria: January 9, 2014
• Last Verified: October 1, 2008

More Information

Terms related to this study

• Keywords: unspecified childhood solid tumor, protocol specific; childhood Burkitt lymphoma; stage III childhood small noncleaved cell lymphoma; stage IV childhood small noncleaved cell lymphoma; stage IV childhood large cell lymphoma; recurrent childhood small noncleaved cell lymphoma; recurrent childhood large cell lymphoma; de novo myelodysplastic syndromes; previously treated myelodysplastic syndromes; secondary myelodysplastic syndromes; childhood acute lymphoblastic leukemia in remission; juvenile myelomonocytic leukemia; chronic phase chronic myelogenous leukemia; childhood chronic myelogenous leukemia; childhood myelodysplastic syndromes; recurrent/refractory childhood Hodgkin lymphoma; relapsing chronic myelogenous leukemia; previously treated childhood rhabdomyosarcoma; recurrent childhood rhabdomyosarcoma; disseminated neuroblastoma; recurrent neuroblastoma; recurrent childhood acute lymphoblastic leukemia; stage III childhood large cell lymphoma; stage III childhood lymphoblastic lymphoma; stage IV childhood lymphoblastic lymphoma; regional neuroblastoma; stage IV childhood Hodgkin lymphoma; recurrent childhood acute myeloid leukemia; recurrent childhood lymphoblastic lymphoma; stage III childhood Hodgkin lymphoma; metastatic Ewing sarcoma/peripheral primitive neuroectodermal tumor; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor; Fanconi anemia; previously untreated childhood rhabdomyosarcoma; childhood Langerhans cell histiocytosis
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Respiratory Tract Diseases; Immune System Diseases; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lung Diseases; Kidney Diseases; Urologic Diseases; Neoplasms, Glandular and Epithelial; Disease; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Anemia; DNA Repair-Deficiency Disorders; Precancerous Conditions; Lung Diseases, Interstitial; Anemia, Hypoplastic, Congenital; Anemia, Aplastic; Congenital Bone Marrow Failure Syndromes; Bone Marrow Failure Disorders; Renal Tubular Transport, Inborn Errors; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Sarcoma; Lymphoma; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Fanconi Syndrome; Fanconi Anemia; Neuroblastoma; Histiocytosis, Langerhans-Cell; Histiocytosis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antirheumatic Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Methylprednisolone; Cyclophosphamide; Melphalan; Fludarabine; Fludarabine phosphate; Busulfan; Antilymphocyte Serum
• Other Study ID Numbers: CDR0000365544; PSCI-2003-232