Neuroblastoma Vaccine for Treatment of High-Risk Neuroblastoma After Chemotherapy (CYCHE2)

This study has been completed.
Sponsor:
Collaborators:
Texas Children's Hospital
Center for Cell and Gene Therapy, Baylor College of Medicine
Information provided by (Responsible Party):
Malcolm Brenner, Baylor College of Medicine
ClinicalTrials.gov Identifier:
NCT00048386
First received: October 30, 2002
Last updated: July 26, 2012
Last verified: July 2012
  Purpose

PRIMARY OBJECTIVE To determine the percentage of patients with high risk neuroblastoma in first or subsequent partial response or better, or with microscopic residual bone marrow disease, who demonstrate an immunological anti-tumor response at any time during, and for up to 12 months from initiation of, treatment with subcutaneous injections of autologous neuroblastoma cells, genetically modified by adenoviral vectors to secrete interleukin-2 (IL-2) (autologous neuroblastoma vaccine)

SECONDARY OBJECTIVES 1. To determine the toxicity of the autologous neuroblastoma vaccine given according to this schedule 2. To obtain preliminary data on the effect of vaccine administration on progression-free survival from high-risk neuroblastoma


Condition Intervention Phase
Neuroblastoma
Biological: autologous neuroblastoma vaccine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Gene Modified Autologous Neuroblastoma Vaccine for the Post-Chemotherapy Treatment of High-Risk Neuroblastoma

Resource links provided by NLM:


Further study details as provided by Baylor College of Medicine:

Primary Outcome Measures:
  • Patients who demonstrate immunological anti-tumor response at any time during, and for up to 12 months from initiation of, treatment with injections of autologous neuroblastoma cells, genetically modified by adenoviral vectors to secrete IL-2 [ Time Frame: 12 months post injections ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the toxicity of the autologous neuroblastoma vaccine given according to this schedule [ Time Frame: 15 years ] [ Designated as safety issue: Yes ]
  • To obtain preliminary data on progression-free survival from high-risk neuroblastoma following vaccine administration [ Time Frame: 15 years ] [ Designated as safety issue: No ]

Enrollment: 13
Study Start Date: November 1999
Study Completion Date: October 2009
Primary Completion Date: December 2004 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: autologous neuroblastoma vaccine
    A vaccine dose of 0.3 x 108 IL-2 secreting cells/patient/injection will be used. Injections will be given twice monthly for two months, then monthly for four months, for a total of eight vaccine injections over six months.
Detailed Description:

Tumor cells from subjects with high-risk neuroblastoma will be obtained at the time of presentation and initial diagnosis, during routine surveillance of bone marrow disease status, or at the time of surgical resection of disease during primary chemotherapy. The tumor cells will be irradiated to prevent the possibility of tumor growth. Autologous neuroblastoma tumor cells will be used to treat neuroblastoma following the completion of primary or salvage chemotherapy when peripheral blood lymphocyte counts have recovered to > 500 CD3+ cells/mm3. This preceding chemotherapy may or may not have included bone marrow or peripheral stem cell rescue. Therefore, following the achievement of best response with chemotherapy, vaccine will be administered for 6 months. Vaccine modified for secretion of IL-2 will be used.

Vaccine therapy will commence after complete recovery from the side effects of primary or salvage chemotherapy, as long as the subject has an absolute CD3+ lymphocyte count and an absolute neutrophil count greater than 500/mm3. A vaccine consisting of 0.3 x 10 8 cells/patient will be given per injection, based on data from the Phase I studies. Injections will be given twice monthly for two months, then monthly for four months, for a total of eight vaccine injections over six months. The immune effects of the vaccine, toxicity of treatment, and anti-tumor effects will be periodically assessed. Further evaluation will be done annually.

The first and second vaccine injection sites will be "punch biopsied" one week after the injection. Several x-rays and various types of scans will also be taken to assist with monitoring the status of the neuroblastoma. Complete details of the evaluations required by this study are included in.

Subjects may receive supportive care for any acute or chronic toxicity from the injections, including blood product support, antibiotics, and other appropriate intervention. Pneumocystis carinii prophylaxis initiated during chemotherapy may be continued during vaccine therapy for as long as deemed appropriate by the investigator. As well, subjects may receive concurrent therapy with cis-retinoic acid at the discretion of the treating physician.

An adenoviral vector is being used to transduce the cells ex-vivo. Subjects will not be treated with the viral vector.

  Eligibility

Ages Eligible for Study:   up to 64 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

  • Patients with high risk neuroblastoma defined below, who, following completion of front-line or salvage chemotherapy that may or may not have included high-dose chemotherapy followed by peripheral blood stem cell or bone marrow rescue with or without cis-retinoic acid, have achieved partial response or better, or who have microscopic residual bone marrow:

    1. INSS Stage 4 neuroblastoma, diagnosed between 1 and 21 years of age (inclusive)
    2. INSS Stage 3, N-myc amplified neuroblastoma, diagnosed between 1 and 21 years of age (inclusive)
    3. INSS Stage 3, N-myc non-amplified, Shimada unfavorable histology neuroblastoma, diagnosed between 1 and 21 years of age (inclusive)
    4. INSS Stages 2A or 2B, N-myc amplified, Shimada unfavorable histology, diagnosed between 1 and 21 years of age (inclusive)
    5. INSS Stage 4 neuroblastoma, with Shimada unfavorable histology, diagnosed under 365 days of age
  • Patients with intermediate or low risk neuroblastoma, who have achieved a second or subsequent partial response or better following chemotherapy treatment of first or subsequent relapse
  • Patients must have recovered from the toxic effects of prior chemotherapy prior to treatment on this study, and must have both an absolute lymphocyte count and an absolute neutrophil count greater than 500/mm3.
  • Patients with disease status outlined in the first bullet who have been treated with allogeneic tumor vaccine are eligible for treatment with autologous tumor vaccine when that product becomes available
  • Patients may not concurrently receive any investigational agents or other tumor vaccines.
  • Patients must be HIV-negative.
  • Female patients must not be pregnant or lactating.
  • Patients must have autologous transduced neuroblastoma cells available that are demonstrably producing > 150 pg IL-2/10e6 cells/24 hours.
  • Patients or legal guardians must sign an informed consent according to institutional guidelines.
  • Patients who are sexually active must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom.
  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: NCT00048386

Locations
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Sponsors and Collaborators
Malcolm Brenner
Texas Children's Hospital
Center for Cell and Gene Therapy, Baylor College of Medicine
Investigators
Principal Investigator: Heidi V Russell, MD Baylor College of Medicine
  More Information

No publications provided

Responsible Party: Malcolm Brenner, Professor Departments of Medicine and Pediatrics/Director Center for Cell and Gene Therapy, Baylor College of Medicine
ClinicalTrials.gov Identifier: NCT00048386     History of Changes
Other Study ID Numbers: H8354, HIGH RISK NEUROBLASTOMA
Study First Received: October 30, 2002
Last Updated: July 26, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Neuroblastoma
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on September 30, 2014