N99-01: Combination Chemotherapy, Radiation Therapy, and Stem Cell Transplantation in Treating Patients With Neuroblastoma

Sponsor

New Approaches to Neuroblastoma Therapy Consortium (Other)

Overall Status

Completed

CT.gov ID

NCT00005978

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Giving the drugs in different ways may kill more tumor cells. Radiation therapy uses high-energy x-rays to damage tumor cells. Peripheral stem cell or bone marrow transplantation may be able to replace immune cells that were destroyed by chemotherapy or radiation therapy.

PURPOSE: This phase I trial is studying the side effects and best dose of combination chemotherapy when given before stem cell transplant and radiation therapy in treating patients with neuroblastoma that has not responded to previous treatments.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma	Biological: filgrastim Drug: carboplatin Drug: etoposide Drug: melphalan Procedure: autologous bone marrow transplantation Procedure: peripheral blood stem cell transplantation Radiation: iobenguane I 131 Radiation: radiation therapy	Phase 1

Detailed Description

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

May 1, 2000

Actual Primary Completion Date :

Dec 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Los Angeles	Los Angeles	California	United States	90027-0700
2	Lucile Packard Children's Hospital at Stanford University Medical Center	Palo Alto	California	United States	94304
3	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94143
4	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus	Atlanta	Georgia	United States	30322
5	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
6	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5289
7	Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support	Bethesda	Maryland	United States	20892-1182
8	Children's Hospital Boston	Boston	Massachusetts	United States	02115
9	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
10	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0914
11	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
12	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
13	Texas Children's Cancer Center	Houston	Texas	United States	77030-2399
14	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
15	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164