Biological Therapy in Treating Children With Refractory or Recurrent Neuroblastoma or Other Tumors

Sponsor

Children's Oncology Group (Other)

Overall Status

Completed

CT.gov ID

NCT00003750

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Locations

Arm

Duration (Months)

0.5

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

RATIONALE: Biological therapies such as hu14.18-interleukin-2 fusion protein use different ways to stimulate the immune system and stop cancer cells from growing.

PURPOSE: Phase I trial to study the effectiveness of hu14.18-interleukin-2 fusion protein in treating children who have refractory or recurrent neuroblastoma or other tumors.

Condition or Disease	Intervention/Treatment	Phase
Melanoma (Skin) Neuroblastoma Sarcoma Unspecified Childhood Solid Tumor, Protocol Specific	Biological: hu14.18-IL2 fusion protein	Phase 1

Detailed Description

OBJECTIVES:

Determine the maximum tolerated dose of hu14.18-interleukin-2 fusion protein in children with refractory or recurrent neuroblastoma or other GD2-positive tumors.
Determine the toxicity and pharmacokinetics of the fusion protein in these patients.
Determine the effect of the fusion protein on systemic immune modulation in these patients.
Quantitate the antifusion protein antibodies in patients treated with fusion protein.
Evaluate antitumor responses resulting from this fusion protein regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive hu14.18-interleukin-2 (hu14.18-IL2) fusion protein IV over 4 hours once daily on days 1-3. Treatment repeats every 28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of hu14.18-IL2 fusion protein until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed every 2 months for 1 year, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study within 1 year.

Study Design

Study Type:

Interventional

Actual Enrollment :

28 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase I/IB Intergroup Trial of the HU14.18-IL2 Fusion Protein in Children With Refractory Neuroblastoma and Other GD2 Positive Tumors

Study Start Date :

Oct 1, 2001

Actual Primary Completion Date :

Jan 1, 2005

Actual Study Completion Date :

Sep 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DG2 positive relapsed or refractory solid tumors The initial hu14.18-IL2 fusion protein (FP) dose will be 2 mg/m2 given intravenously over 4 hours, daily for 3 days. Five separate dose levels are scheduled: 2 mg/m²/dose (IV over 4 hours) x 3 days, 4 mg/m²/dose (IV over 4 hours) x 3 days, 6 mg/m²/dose (IV over 4 hours) x 3 days, 8 mg/m²/dose (IV over 4 hours) x 3 days, 10 mg/m²/dose (IV over 4 hours) x 3 days.	Biological: hu14.18-IL2 fusion protein

Arm

Intervention/Treatment

Experimental: DG2 positive relapsed or refractory solid tumors

The initial hu14.18-IL2 fusion protein (FP) dose will be 2 mg/m2 given intravenously over 4 hours, daily for 3 days. Five separate dose levels are scheduled: 2 mg/m²/dose (IV over 4 hours) x 3 days, 4 mg/m²/dose (IV over 4 hours) x 3 days, 6 mg/m²/dose (IV over 4 hours) x 3 days, 8 mg/m²/dose (IV over 4 hours) x 3 days, 10 mg/m²/dose (IV over 4 hours) x 3 days.

Biological: hu14.18-IL2 fusion protein

Outcome Measures

Primary Outcome Measures

Determine the MTD and pharmacokinetics of hu14.18-IL2 fusion protein []
Determine the MTD of hu14.18-IL2 fusion protein and determine the pharmacokinetics of the fusion protein when given as I.V. injections

Secondary Outcome Measures

Assess immunological changes associated with fusion protein therapy []

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 21 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically confirmed neuroblastoma or melanoma at original diagnosis
Refractory to chemotherapy or recurrence after prior multiagent chemotherapy
Measurable or evaluable (detectable by bone scan) metastatic disease OR
No evidence of disease if complete response to prior surgical resection, radiotherapy, and/or chemotherapy OR
Histologically confirmed tumor expressing GD2 antigen at original diagnosis or relapse
Refractory to standard treatment
Measurable or evaluable disease by clinical assessments or laboratory markers OR
No evidence of disease after prior surgical resection of metastatic, recurrent disease
Histologically confirmed recurrent osteogenic sarcoma after prior chemotherapy allowed
Soft tissue sarcoma allowed
No primary CNS tumors
Prior CNS metastases allowed, provided:
Disease previously treated
Disease clinically stable for 4 weeks before study
At least 4 weeks since prior steroids for CNS metastases
No clinically detectable pleural effusions or ascites

PATIENT CHARACTERISTICS:

Age:

21 and under

Performance status:

Karnofsky 60-100% for children over age 10
Lansky 60-100% for children age 10 and under

Life expectancy:

At least 12 weeks

Hematopoietic:

Absolute neutrophil count greater than 1,000/mm^3
Platelet count at least 75,000/mm^3 (transfusion allowed)
Hemoglobin at least 9.0 g/dL (transfusion allowed)

Hepatic:

Bilirubin less than 1.5 mg/dL
ALT or AST no greater than 2.5 times normal
Hepatitis B surface antigen negative

Renal:

Creatinine no greater than 1.5 mg/dL OR
Creatinine clearance or radioisotope glomerular filtration rate at least 60 mL/min

Cardiovascular:

Shortening fraction at least 27% by echocardiogram OR
Ejection fraction more than 50% by MUGA scan
No congestive heart failure
No uncontrolled cardiac rhythm disturbance

Pulmonary:

FEV_1 and FVC more than 60% of predicted OR
No dyspnea at rest
No exercise intolerance
Oxygen saturation more than 94% by pulse oximetry on room air

Neurologic:

No seizure disorders requiring antiseizure medications
No significant neurologic deficit or grade 2 or greater objective peripheral neuropathy

Other:

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
HIV negative
No significant concurrent illnesses unrelated to cancer or its treatment
No significant psychiatric disabilities
No uncontrolled active infections
No uncontrolled active peptic ulcer

PRIOR CONCURRENT THERAPY:

Biologic therapy:

At least 1 week since prior growth factors
At least 1 week since prior immunomodulatory therapy
Prior monoclonal antibodies allowed if no detectable antibody to hu14.18
Prior autologous bone marrow transplantation (BMT) or stem cell transplantation (SCT) allowed
Prior autologous BMT or SCT with monoclonal antibody-purged specimens allowed
No concurrent growth factors
No concurrent interferon

Chemotherapy:

See Disease Characteristics
At least 3 weeks since prior chemotherapy (6 weeks for nitrosoureas, mitomycin, or melphalan)
No concurrent palliative chemotherapy

Endocrine therapy:

See Disease Characteristics
At least 2 weeks since prior glucocorticoids, except for life-threatening symptoms
No concurrent corticosteroids
No concurrent glucocorticoids, except for life-threatening symptoms

Radiotherapy:

See Disease Characteristics
At least 3 weeks since prior radiotherapy
No concurrent palliative radiotherapy

Surgery:

See Disease Characteristics
At least 2 weeks since prior major surgery (e.g., laparotomy or thoracotomy)
No prior organ allografts
No concurrent palliative surgery

Other:

Recovered from prior therapy
At least 1 week since prior tretinoin
At least 3 weeks since prior immunosuppressive therapy
No other concurrent immunosuppressive drugs

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202-3591
2	University of Arkansas for Medical Sciences	Little Rock	Arkansas	United States	72205
3	City of Hope Comprehensive Cancer Center	Duarte	California	United States	91010-3000
4	Rebecca and John Moores UCSD Cancer Center	La Jolla	California	United States	92093-0658
5	Children's Hospital Los Angeles	Los Angeles	California	United States	90027-0700
6	Jonsson Comprehensive Cancer Center, UCLA	Los Angeles	California	United States	90095-1781
7	Children's Hospital of Orange County	Orange	California	United States	92868
8	UCSF Comprehensive Cancer Center	San Francisco	California	United States	94115
9	Stanford Cancer Center at Stanford University Medical Center	Stanford	California	United States	94305-5208
10	Children's National Medical Center	Washington	District of Columbia	United States	20010-2970
11	Shands Cancer Center at the University of Florida Health Science Center	Gainesville	Florida	United States	32610-0296
12	AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Scottish RiteCampus	Atlanta	Georgia	United States	30342
13	Children's Memorial Hospital - Chicago	Chicago	Illinois	United States	60614
14	Indiana University Cancer Center	Indianapolis	Indiana	United States	46202-5289
15	Kansas Cancer Institute at the University of Kansas Medical Center	Kansas City	Kansas	United States	66160-7357
16	MBCCOP - LSU Health Sciences Center	New Orleans	Louisiana	United States	70112
17	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
18	Floating Hospital for Children	Boston	Massachusetts	United States	02111
19	Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute	Boston	Massachusetts	United States	02115
20	University of Michigan Comprehensive Cancer Center	Ann Arbor	Michigan	United States	48109-0914
21	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
22	University of Minnesota Cancer Center	Minneapolis	Minnesota	United States	55455
23	Mayo Clinic Cancer Center	Rochester	Minnesota	United States	55905
24	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216-4505
25	Children's Mercy Hospital	Kansas City	Missouri	United States	64108
26	Cardinal Glennon Children's Hospital	Saint Louis	Missouri	United States	63104
27	Washington University Medical Center	Saint Louis	Missouri	United States	63105
28	Cancer Center at Hackensack University Medical Center	Hackensack	New Jersey	United States	07601
29	Robert Wood Johnson Medical School	New Brunswick	New Jersey	United States	08901
30	NYU School of Medicine's Kaplan Comprehensive Cancer Center	New York	New York	United States	10016
31	Memorial Sloan-Kettering Cancer Center	New York	New York	United States	10021
32	Herbert Irving Comprehensive Cancer Center at Columbia University	New York	New York	United States	10032
33	University Hospital at State University of New York - Upstate Medical University	Syracuse	New York	United States	13210
34	Duke Comprehensive Cancer Center	Durham	North Carolina	United States	27710
35	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229-3039
36	Children's Hospital of Columbus	Columbus	Ohio	United States	43205-2696
37	Oklahoma University Medical Center at University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73126
38	CCOP - Columbia River Oncology Program	Portland	Oregon	United States	97225
39	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
40	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
41	Hollings Cancer Center at Medical University of South Carolina	Charleston	South Carolina	United States	29425-0721
42	St. Jude Children's Research Hospital	Memphis	Tennessee	United States	38105-2794
43	Vanderbilt-Ingram Cancer Center at Vanderbilt Medical Center	Nashville	Tennessee	United States	37232-6838
44	Simmons Cancer Center at University of Texas Southwestern Medical Center - Dallas	Dallas	Texas	United States	75390-9063
45	Cook Children's Medical Center - Fort Worth	Fort Worth	Texas	United States	76104
46	Texas Children's Cancer Center	Houston	Texas	United States	77030-2399
47	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030-4009
48	University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78207
49	CCOP - Scott and White Hospital	Temple	Texas	United States	76508
50	Huntsman Cancer Institute	Salt Lake City	Utah	United States	84112
51	Children's Hospital and Regional Medical Center - Seattle	Seattle	Washington	United States	98105
52	University of Wisconsin Comprehensive Cancer Center	Madison	Wisconsin	United States	53792-6164
53	CCOP - Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States	54449
54	Midwest Children's Cancer Center	Milwaukee	Wisconsin	United States	53226
55	Royal Children's Hospital	Parkville	Victoria	Australia	3052
56	Princess Margaret Hospital for Children	Perth	Western Australia	Australia	6001
57	Hospital for Sick Children	Toronto	Ontario	Canada	M5G 1X8
58	McGill University Health Center - Montreal Children's Hospital	Montreal	Quebec	Canada	H3G 1A4
59	Hopital Sainte Justine	Montreal	Quebec	Canada	H3T 1C5