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Phase I Study to Evaluate the Safety of Cellular Immunotherapy for Recurrent/Refractory Neuroblastoma Using Genetically-Modified Autologous CD8+ T Cell Clones


Phase 1
1 Year
17 Years
Not Enrolling
Both
Neuroblastoma

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Trial Information

Phase I Study to Evaluate the Safety of Cellular Immunotherapy for Recurrent/Refractory Neuroblastoma Using Genetically-Modified Autologous CD8+ T Cell Clones


OBJECTIVES: I. Determine the safety and toxicity of cellular immunotherapy using ex vivo
expanded autologous CD8+ cytotoxic T-lymphocyte clones genetically modified to express the
CE7R scFvFc:zeta chimeric immunoreceptor and the HyTK selection/suicide gene in children
with recurrent or refractory disseminated neuroblastoma. II. Determine the antitumor
activity of this regimen in these patients. III. Determine the duration of in vivo
persistence of adoptively transferred clones and the effect of interleukin-2 on maintaining
the in vivo persistence of these clones. IV. Screen for the development of host
anti-scFvFc:zeta and HyTK immune responses in patients treated with this regimen. V.
Determine the efficacy of ganciclovir in ablating transferred clones in vivo if toxicity
occurs in these patients.

OUTLINE: This is a multicenter study. Patients undergo autologous peripheral blood stem cell
harvest. CD8+ cytotoxic T-lymphocyte (CTL) clones are isolated, genetically modified to
express the CE7R scFvFc:zeta chimeric immunoreceptor and the HyTK selection/suicide gene,
and then expanded ex vivo. While the modified CTL clones are being generated, patients each
receive an individualized salvage chemotherapy regimen that may consist of one of the
following: cyclophosphamide and topotecan; ifosfamide, carboplatin, and etoposide; or
another chemotherapy regimen chosen by the patient's primary oncologist. The first cohort of
5 patients receives escalating doses of modified CTL clones IV over 30 minutes on days 0,
14, and 28 in the absence of disease progression or unacceptable toxicity. Each patient
begins the series of 3 infusions as soon as an adequate number of modified CTL clones are
ready and after the acute side effects of chemotherapy have resolved. In the absence of
unacceptable toxicity in the first cohort, the second cohort of 5 patients receives the same
treatment as cohort 1 plus interleukin-2 subcutaneously every 12 hours on days 15-24 and
29-38. Patients with unacceptable toxicity receive ganciclovir IV every 12 hours for 14 days
(or longer if symptomatic resolution is not achieved in that interval). Patients are
followed at day 100 and then periodically thereafter.

PROJECTED ACCRUAL: A total of 10 patients will be accrued for this study within 3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS: Histologically and/or radiographically proven disseminated
neuroblastoma Recurrent or refractory to first-line therapy as defined by less than
complete response to standard induction chemotherapy combined with surgical resection
Histologic verification of neuroblastoma required at original diagnosis No
radiographically detectable CNS involvement No clinically evident progressive
encephalopathy

PATIENT CHARACTERISTICS: Age: 1 to 17 (children only) Performance status: Not specified
Life expectancy: At least 3 months Hematopoietic: Not specified Hepatic: Not specified
Renal: No dialysis dependency Cardiovascular: No uncontrolled cardiac arrhythmia No
hypertension requiring pressor support Pulmonary: No requirement for supplemental oxygen
unless expected to resolve within 2 weeks Neurologic: See Disease Characteristics No
refractory seizure disorder Other: No detectable human antimouse antibody reactivity if
received prior murine antibody preparations No history of ganciclovir allergy or
intolerance HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients
must use effective contraception during and for at least 2 months after study

PRIOR CONCURRENT THERAPY: Biologic therapy: No other concurrent antibody therapy during or
after study No other concurrent immunotherapy (e.g., interferons, vaccines, or other
cellular products) Chemotherapy: At least 3 weeks since prior standard or experimental
chemotherapy and recovered Endocrine therapy: No concurrent systemic corticosteroids
unless specifically for amelioration of toxicity induced by transferred T-cell therapy
Radiotherapy: Not specified Surgery: Not specified Other: At least 3 weeks since prior
immunosuppressive therapies and recovered No concurrent pentoxifylline No other concurrent
investigational agents No concurrent ganciclovir, any ganciclovir derivatives, or
acyclovir for non-life-threatening herpes virus infections

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Julie R. Park, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center

Authority:

United States: Federal Government

Study ID:

1524.00

NCT ID:

NCT00006480

Start Date:

May 2000

Completion Date:

March 2005

Related Keywords:

  • Neuroblastoma
  • disseminated neuroblastoma
  • recurrent neuroblastoma
  • Neuroblastoma

Name

Location

Fred Hutchinson Cancer Research CenterSeattle, Washington  98109
Cancer Center and Beckman Research Institute, City of HopeDuarte, California  91010-3000