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Dose Escalation Study of 131 I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma - A Phase I Study


Phase 1
1 Year
21 Years
Not Enrolling
Both
Neuroblastoma

Thank you

Trial Information

Dose Escalation Study of 131 I-Metaiodobenzylguanidine (MIBG) With Intensive Chemotherapy and Autologous Stem Cell Rescue for High-Risk Neuroblastoma - A Phase I Study


OBJECTIVES:

- Determine the maximum tolerated dose and toxic effects of iodine I 131
metaiodobenzylguanidine (131 I-MIBG) plus ablative doses of carboplatin and etoposide
administered with fixed-dose melphalan followed by autologous hematopoietic stem cell
transplantation in patients with refractory or residual high-risk neuroblastoma.

- Determine the number of days until blood counts recover in these patients after
receiving this treatment regimen.

- Determine the response rate to this treatment regimen in these patients.

- Determine the tumor dosimetry of 131 I-MIBG in patients with measurable soft tissue
lesions.

OUTLINE: This is a dose-escalation study of iodine I 131 metaiodobenzylguanidine (131
I-MIBG), carboplatin, and etoposide. Patients are stratified according to glomerular
filtration rate (at least 100 mL/min vs 60-99 mL/min).

Patients undergo peripheral blood stem cell harvest or bone marrow harvest at least 2 weeks
prior to treatment with 131 I-MIBG.

Patients receive 131 I-MIBG IV over 120 minutes on day -21; melphalan IV on days -7 to -5;
carboplatin and etoposide IV continuously over 96 hours on days -7 to -4; autologous
hematopoietic stem cell transplantation IV over 15-30 minutes on day 0; and filgrastim
(G-CSF) subcutaneously or IV starting on day 0 and continuing until blood counts recover.
Radiotherapy is administered to the primary tumor site and metastatic sites twice daily for
7 consecutive days within 6 weeks of transplantation or once blood counts have recovered.

Cohorts of 3-6 patients receive escalating doses of 131 I-MIBG, carboplatin, and etoposide
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed at day 84, and then 2 months later if there is a complete response
and/or partial response. Patients who continue therapy on other protocols are followed
before starting the new therapy. All patients are followed for life for any delayed toxic
effects related to study therapy, secondary malignancies, disease status, and survival.

PROJECTED ACCRUAL: A total of 30-60 patients (15-30 per stratum) will be accrued for this
study within 2-3 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Diagnosis of neuroblastoma as evidenced by one of the following:

- Histological confirmation

- Demonstrates clumps of tumor cells in bone marrow with elevated urinary
catecholamine metabolites

- High-risk refractory or residual disease

- Poorly responding disease, meeting 1 of the following criteria:

- Stable disease or partial response after at least 12 weeks of induction therapy

- Bone marrow containing greater than 100 tumor cells per 100,000 normal cells
after 12 weeks of induction therapy

- Progressive disease during or after therapy

- At least 1 prior positive iodine I 131 metaiodobenzylguanidine (131 I-MIBG) scan
since diagnosis and meets disease status criteria

PATIENT CHARACTERISTICS:

Age:

- 1 to 21 (1 to 20 at diagnosis)

Performance status:

- ECOG 0-2

Life expectancy:

- At least 2 months

Hematopoietic:

- Absolute neutrophil count at least 500/mm^3

- Platelet count at least 20,000/mm^3 (transfusion allowed)

- Hemoglobin at least 8 g/dL (transfusion allowed)

Hepatic:

- Bilirubin normal

- AST/ALT no greater than 3 times normal

- No active hepatitis (for HIV-positive patients only)

Renal:

- Glomerular filtration rate or creatinine clearance at least 60 mL/min

- Creatinine less than 1.5 times normal for age

Cardiovascular:

- Ejection fraction at least 55% OR

- Fractional shortening at least 30%

Pulmonary:

- No dyspnea at rest or exercise intolerance

- No requirement for supplemental oxygen

- No active pneumonia (for HIV-positive patients only)

Other:

- No disease of any major organ system that would preclude study participation

- No other active health problems (for HIV-positive patients only)

- No active infections requiring intravenous antivirals, antibiotics, or antifungals

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

- At least 3 weeks since prior biologic therapy and recovered

Chemotherapy:

- At least 3 weeks since prior chemotherapy and recovered

- No more than 100 mg/m^2 total dose of prior melphalan

Endocrine therapy:

- Not specified

Radiotherapy:

- No prior total body, whole abdominal, or whole liver irradiation

- No prior therapy with 131 I-MIBG

- At least 2 weeks since prior radiotherapy (6 months for prior radiotherapy to
craniospinal or whole lung fields or greater than 50% of bone marrow space) and
recovered

Surgery:

- Prior surgical resection allowed

- Recovered from prior surgery

Other:

- No prior myeloablative therapy

- Prior submyeloablative therapy with peripheral blood stem cell support allowed

- No concurrent antiretrovirals for HIV-positive patients

- Concurrent prolonged antifungal allowed if culture and biopsy negative in suspected
residual radiographic lesions

- No medications that may preclude uptake of 131 I-MIBG for 1 week prior and 2 weeks
after administration of study drugs

- No concurrent hemodialysis

Type of Study:

Interventional

Study Design:

Primary Purpose: Treatment

Principal Investigator

Katherine K. Matthay, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Children's Hospital Los Angeles

Authority:

United States: Food and Drug Administration

Study ID:

CDR0000067966

NCT ID:

NCT00005978

Start Date:

May 2000

Completion Date:

Related Keywords:

  • Neuroblastoma
  • localized resectable neuroblastoma
  • regional neuroblastoma
  • disseminated neuroblastoma
  • stage 4S neuroblastoma
  • recurrent neuroblastoma
  • localized unresectable neuroblastoma
  • Neuroblastoma

Name

Location

University of Michigan Comprehensive Cancer CenterAnn Arbor, Michigan  48109-0752
Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Indiana University Cancer CenterIndianapolis, Indiana  46202-5265
University of Wisconsin Comprehensive Cancer CenterMadison, Wisconsin  53792
Children's Hospital Los AngelesLos Angeles, California  90027-0700
Children's Hospital and Regional Medical Center - SeattleSeattle, Washington  98105
Children's Memorial Hospital - ChicagoChicago, Illinois  60614
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer InstituteBoston, Massachusetts  02115
Texas Children's Cancer CenterHouston, Texas  77030-2399
UCSF Comprehensive Cancer CenterSan Francisco, California  94115
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Lucile Packard Children's Hospital at Stanford University Medical CenterPalo Alto, California  95798
AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston CampusAtlanta, Georgia  30322
Warren Grant Magnuson Clinical Center - NCI Clinical Studies SupportBethesda, Maryland  20892-1182
Children's Hospital BostonBoston, Massachusetts  02115