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Busulfan, Melphalan, and Antithymocyte Globulin Followed By Umbilical Cord Blood Transplant in Treating Young Patients With Refractory or Relapsed Malignant Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00436761
Recruitment Status : Unknown
Verified June 2007 by National Cancer Institute (NCI).
Recruitment status was:  Active, not recruiting
First Posted : February 19, 2007
Last Update Posted : December 18, 2013
Information provided by:
National Cancer Institute (NCI)

Brief Summary:

RATIONALE: Giving chemotherapy before a donor umbilical cord blood stem cell transplant helps stop the growth of tumor cells. It also helps stop the patient's immune system from rejecting the donor's stem cells when they do not exactly match the patient's blood. The donated stem cells may replace the patient's immune cells and help destroy any remaining tumor cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving cyclosporine and methylprednisolone after the transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects of busulfan, melphalan, and antithymocyte globulin followed by umbilical cord blood transplant in treating young patients with refractory or relapsed malignant solid tumors.

Condition or disease Intervention/treatment Phase
Unspecified Childhood Solid Tumor, Protocol Specific Biological: anti-thymocyte globulin Biological: graft-versus-tumor induction therapy Biological: sargramostim Drug: busulfan Drug: cyclosporine Drug: melphalan Drug: methylprednisolone Other: flow cytometry Other: immunologic technique Other: laboratory biomarker analysis Procedure: allogeneic hematopoietic stem cell transplantation Procedure: umbilical cord blood transplantation Phase 1

Detailed Description:


  • Examine the impact of the use of killer cell immunoglobulin-like receptor (KIR)-mismatched umbilical cord blood as a source of hematopoietic stem cells, after busulfan, melphalan, and anti-thymocyte globulin in pediatric patients with relapsed or refractory solid tumors.
  • Determine the toxicity of this regimen, in terms of incidence of grade 3-4 acute graft-versus-host disease, donor/host chimerism, and cellular immunity against tumor cell lines, in these patients.


  • Transplantation: Patients receive busulfan orally or IV every 6 hours on days -8 to -5, anti-thymocyte globulin IV over 6 hours on days -4 to -1, and melphalan IV over 15-20 minutes on days -4 to -2. Patients undergo allogeneic umbilical cord blood stem cell infusion on day 0. Patients receive sargramostim (GM-CSF) subcutaneously beginning on day 7 and continuing until blood counts recover.
  • Graft-vs-host disease prophylaxis: Patients receive cyclosporine IV over 1 hour or orally twice daily on days -1 to 180 and methylprednisolone IV or orally once or twice daily on days 5 - 49.

Blood samples are collected periodically for immunophenotyping and flow cytometric analysis (including interferon gamma and other TH1 and TH2 cytokines).

After completion of study treatment, patients are followed periodically.

PROJECTED ACCRUAL: A total of 20 patients will be accrued for this study.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I Study to Examine the Toxicity of Killer IG-Like Receptor (KIR) Mismatched Umbilical Cord Blood for Pediatric Patients With Malignant Solid Tumors
Study Start Date : May 2004

Primary Outcome Measures :
  1. Safety
  2. Incidence of graft-versus-host disease

Secondary Outcome Measures :
  1. Donor/host chimerism status
  2. Immune function post-transplant

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of malignant solid tumor
  • Relapsed or refractory disease

    • No isolated local recurrence of disease (in the site of the primary tumor) > 1 year after completing therapy
  • No brain tumors or brain metastases
  • Unrelated cord blood donor available

    • May be HLA 6/6 matched (HLA-A, -B, -DR) OR mismatched for 1, 2, or 3 of these HLA loci, but must be mismatched for HLA-C group as indicated by their following killer cell immunoglobulin-like receptor (KIR) group specificity:

      • KIR2DL1

        • Cw 2
        • Cw 0307
        • Cw 4, 5, 6
        • Cw 0707, 0709
        • Cw 1204, 1205
        • All other Cw 15 alleles
        • Cw 1602
        • Cw 17
        • Cw 18
      • KIR2DL2

        • Cw 1
        • All other Cw 3 alleles
        • All other Cw 7 alleles
        • Cw 8
        • Cw 1202, 1203, 1206
        • Cw 1301
        • Cw 1402, 1403
        • Cw 1507
        • Cw 1601, 1604
  • Cord blood specimen must have ≥ 1 x 10^7 nucleated cells/kg patient ideal body weight


  • ECOG performance status (PS) 0-2 OR Lansky PS 70-100%
  • Cardiac ejection fraction ≥ 50%
  • Creatinine clearance ≥ 50%
  • Bilirubin ≤ 3.0 mg/dL
  • DLCO ≥ 70% OR O_2 saturation ≥ 95% on room air


  • Prior autologous stem cell transplantation allowed

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00436761

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United States, Pennsylvania
Penn State Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Sponsors and Collaborators
Milton S. Hershey Medical Center
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Study Chair: Kenneth G. Lucas, MD Milton S. Hershey Medical Center
Layout table for additonal information Identifier: NCT00436761    
Other Study ID Numbers: CDR0000529361
First Posted: February 19, 2007    Key Record Dates
Last Update Posted: December 18, 2013
Last Verified: June 2007
Keywords provided by National Cancer Institute (NCI):
unspecified childhood solid tumor, protocol specific
Additional relevant MeSH terms:
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Antilymphocyte Serum
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating