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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 recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2007 by National Cancer Institute (NCI).
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00436761
First received: February 15, 2007
Last updated: December 17, 2013
Last verified: June 2007
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Safety [ Designated as safety issue: Yes ]
  • Incidence of graft-versus-host disease [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Donor/host chimerism status [ Designated as safety issue: No ]
  • Immune function post-transplant [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: May 2004
Detailed Description:

OBJECTIVES:

  • 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.

OUTLINE:

  • 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.

  Eligibility

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

DISEASE CHARACTERISTICS:

  • 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

PATIENT CHARACTERISTICS:

  • 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 CONCURRENT THERAPY:

  • Prior autologous stem cell transplantation allowed
  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: NCT00436761

Locations
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
Investigators
Study Chair: Kenneth G. Lucas, MD Milton S. Hershey Medical Center
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00436761     History of Changes
Other Study ID Numbers: CDR0000529361, PSCI-18589
Study First Received: February 15, 2007
Last Updated: December 17, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
unspecified childhood solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
Antilymphocyte Serum
Busulfan
Melphalan
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
Autonomic Agents
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Myeloablative Agonists
Neuroprotective Agents
Peripheral Nervous System Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on November 24, 2014