Donor Stem Cell Transplant in Treating Young Patients With Relapsed or Refractory Solid Tumors

A Phase I Study to Examine the Toxicity of Allogeneic Stem Cell Transplantation for Pediatric Solid Tumors With Relapsed or Therapy Refractory Disease

RATIONALE: A peripheral stem cell, bone marrow, or umbilical cord blood transplant may be able to replace blood-forming cells that were destroyed by chemotherapy and radiation therapy. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving busulfan and melphalan with or without antithymocyte globulin before transplant and cyclosporine with methylprednisolone or methotrexate after transplant may stop this from happening.

PURPOSE: This phase I trial is studying the side effects of donor stem cell transplant in treating young patients with relapsed or refractory solid tumors.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Unspecified Childhood Solid Tumor, Protocol Specific; Neuroblastoma
• Intervention / Treatment: Drug: methotrexate; Drug: methylprednisolone; Biological: anti-thymocyte globulin; Procedure: allogeneic bone marrow transplantation; Drug: busulfan; Procedure: peripheral blood stem cell transplantation; Drug: melphalan; Drug: cyclosporine; Procedure: umbilical cord blood transplantation

Detailed Description

OBJECTIVES:

• Determine the toxicity of allogeneic hematopoietic stem cell transplantation, in terms of the incidence of grade 3-4 acute graft-versus-host disease, in young patients with relapsed or refractory solid tumors.
• Determine the incidence of transplant-related mortality at 100 days post-transplantation in these patients.

OUTLINE:

• Conditioning: Patients receive busulfan IV or orally 4 times daily on days -8 to -5 (a total of 16 doses) and melphalan IV over 15-20 minutes on days -4 to -2. Patients with an unrelated donor also receive anti-thymocyte globulin IV on days -4 to -2.
• Allogeneic hematopoietic stem cell transplantation (SCT): Patients undergo allogeneic hematopoietic SCT on day 0.
• Post-transplant graft-versus-host disease (GVHD) prophylaxis: Patients who undergo cord blood SCT receive cyclosporine and methylprednisolone for graft-versus-host disease (GVHD) prophylaxis. Patients who undergo peripheral blood or bone marrow SCT receive cyclosporine and methotrexate (short course) for GVHD prophylaxis.

After completion of study treatment, patients are followed at 1, 3, 6, and 12 months and then annually thereafter.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 4 years.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033-0850
      • Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 30 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• Diagnosis of relapsed or refractory solid tumor, including, but not limited to, relapsed neuroblastoma, relapsed Ewing's sarcoma, and relapsed rhabdomyosarcoma
• No isolated local disease recurrence at the site of the primary tumor > 1 year after completion of prior therapy
• No brain tumor or brain metastases

• Related or unrelated hematopoietic stem cell donor available, meeting 1 of the following criteria:

  • Matched for HLA-A, -B, -C, -DR, and -DQ (9/10 or 10/10 allelles) (marrow or peripheral blood)

  • Matched for HLA-A, -B, and -DR (5/6 or 6/6 allelles) (cord blood)

    • Cord blood specimen must contain ≥ 2 x 10 ^7 nucleated cells/kg body weight

PATIENT CHARACTERISTICS:

Age

• 30 and under

Performance status

• ECOG 0-1 OR
• Lansky 80-100%

Life expectancy

• Not specified

Hematopoietic

• Not specified

Hepatic

• Bilirubin ≤ 3.0 mg/dL

Renal

• Creatinine clearance ≥ 50 mL/min

Cardiovascular

• Ejection fraction ≥ 50%

Pulmonary

• DLCO ≥ 70% OR
• O_2 saturation ≥ 95% on room air

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior autologous stem cell transplantation allowed

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)

Collaborators and Investigators

• Sponsor: Milton S. Hershey Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Primary Completion (Actual): April 1, 2010
• Study Completion (Actual): February 1, 2011

Study Registration Dates

• First Submitted: June 2, 2005
• First Submitted That Met QC Criteria: June 2, 2005
• First Posted (Estimate): June 3, 2005

Study Record Updates

• Last Update Posted (Estimate): July 18, 2013
• Last Update Submitted That Met QC Criteria: July 17, 2013
• Last Verified: February 1, 2011

More Information

Terms related to this study

• Keywords: unspecified childhood solid tumor, protocol specific; recurrent childhood rhabdomyosarcoma; recurrent neuroblastoma; recurrent Ewing sarcoma/peripheral primitive neuroectodermal tumor
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive; Neuroectodermal Tumors, Primitive, Peripheral; Sarcoma; Neuroblastoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; 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; Dermatologic Agents; Antifungal Agents; Reproductive Control Agents; Abortifacient Agents, Nonsteroidal; Abortifacient Agents; Folic Acid Antagonists; Calcineurin Inhibitors; Methylprednisolone; Melphalan; Methotrexate; Busulfan; Antilymphocyte Serum; Cyclosporine; Cyclosporins
• Other Study ID Numbers: PSCI-20615; CDR0000430441 (Registry Identifier: PDQ (Physician Data Query))