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A Phase I Investigation of IL-12 (NSC 672423)/Pulse IL-2 (Aldesleukin) in Children With Persistent and/or Refractory Neuroblastoma (13623)


Phase 1
3 Years
21 Years
Not Enrolling
Both
Recurrent Neuroblastoma

Thank you

Trial Information

A Phase I Investigation of IL-12 (NSC 672423)/Pulse IL-2 (Aldesleukin) in Children With Persistent and/or Refractory Neuroblastoma (13623)


OBJECTIVES:

I. Define the maximum tolerated dose and dose-limiting toxicity of interleukin-12 with or
without interleukin-2 in patients with refractory or recurrent neuroblastoma.

II. Determine, preliminarily, the antitumor effect of interleukin-12 with or without
interleukin-2 in these patients.

III. Evaluate the immunoregulatory activity of interleukin-12 with or without interleukin-2
in these patients.

IV. Evaluate the antiangiogenic activity of interleukin-12 with or without interleukin-2 in
these patients.

OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to 1 of 2
treatment cohorts.

COHORT A: Patients receive interleukin-12 (IL-12) IV over 5-15 seconds on days 1, 3, 5, 8,
10, and 12.

COHORT B: Patients receive interleukin-2 (IL-2) IV over 15 minutes twice daily on days 1 and
8 and IL-12 IV as in cohort A.

Treatment in both cohorts repeats every 28 days for up to 4 courses in the absence of
disease progression or unacceptable toxicity. Some patients may receive additional courses
at the discretion of the principal investigator.

Cohorts of 3-6 patients in both cohorts receive escalating doses of IL-2 and IL-12 until the
maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at
which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Once the MTD is determined, an additional cohort of 8 patients receives IL-12 and IL-2 at
the MTD.

Patients are followed at 3 weeks.


Inclusion Criteria:



- Diagnosis of neuroblastoma

- Histologically confirmed disease AND/OR disease defined by tumor cells in the
bone marrow and elevated urinary catecholamine metabolites

- Persistent and/or refractory disease, with at least 1 of the following:

- Biopsy-proven residual disease at least 12 weeks after myeloablative therapy

- Progressive disease after nonmyeloablative or myeloablative therapy

- Recurrent disease, evidenced by any of the following:

- Biopsy-proven recurrent soft tissue disease

- Metaiodobenzylguanidine (MIBG)-positive lesions visible on any other imaging
modality or repeat MIBG obtained 2-4 weeks or more apart

- Histologically confirmed bone marrow disease

- Progressive or stable disease after at least 1 prior standard salvage regime

- No clinically significant pleural effusion

- ECOG 0-1

- Life expectancy >= 12 weeks

- Hepatitis A antibody negative

- Hepatitis B surface antigen negative

- Positive hepatitis B titer allowed if patient has been immunized and has no
history of disease

- Hepatitis C virus negative

- No history of congenital or acquired coagulation disorder

- Cardiac function normal by ECG

- No dyspnea at rest

- No exercise intolerance

- Oxygen saturation at least 94% by pulse oximetry

- DLCO greater than 60% of predicted

- FEV1 greater than 70% of predicted

- Negative pregnancy test

- Skull-based bony lesions without space-occupying intracranial extension are allowed

- No prior or concurrent intracranial metastatic disease to the brain parenchyma

- Not pregnant or nursing

- Fertile patients must use effective barrier contraception during and for at least 2
months after study

- No prior hematologic malignancy (including leukemia or lymphoma)

- No history of malignant hyperthermia

- No prior or concurrent autoimmune disease

- No positive direct Coombs testing

- No history of ongoing or intermittent bowel obstruction

- No active infection or other significant systemic illness

- More than 2 weeks since prior fenretinide

- More than 2 weeks since prior 13-cis-retinoic acid

- More than 2 weeks since prior filgrastim (G-CSF) or sargramostim (GM-CSF)

- More than 2 weeks since prior interferons or interleukins

- More than 2 weeks since prior cytokine-fusion proteins

- More than 2 weeks since prior IV immunoglobulin (IVIG)

- No prior interleukin-12

- No concurrent cytokines

- No concurrent fenretinide

- No concurrent 13-cis-retinoic acid

- No other concurrent immunomodulators, including:

- G-CSF and GM-CSF

- Interferons

- Other interleukins

- IVIG

- More than 4 weeks since prior chemotherapy

- No other unstable medical condition or critical illness that would preclude study
participation

- More than 12 weeks since prior myeloablative chemotherapy followed by autologous stem
cell transplantation:

No prior myeloablative chemotherapy followed by allogeneic bone marrow transplantation

- More than 2 weeks since prior growth hormones

- More than 4 weeks since prior systemic corticosteroids

- More than 2 weeks since prior non-corticosteroid hormonal therapy (including oral
birth control pills)

- No concurrent hormonal therapy (including oral birth control pills)

- No concurrent growth hormones

- No concurrent systemic corticosteroids, except for use in life-threatening
complications

- More than 4 weeks since prior radiotherapy

- No prior solid organ transplantation

- More than 4 weeks since prior investigational agents

- No other concurrent investigational agents

- No prior enrollment on COG-A3973, unless disease has progressed

- No history of hemolytic anemia

- Absolute neutrophil count at least 1,500/mm^3 [Note: Independent of growth factor or
transfusion support]

- Platelet count at least 75,000/mm^3 [Note: Independent of growth factor or
transfusion support]

- AST and ALT less than 2.5 times upper limit of normal

- Bilirubin less than 2.0 mg/dL

- Creatinine clearance or radioisotope glomerular filtration rate at least 70 mL/min OR
creatinine normal

- HIV negative

- Ejection fraction at least 50% by echocardiogram or MUGA OR Fractional shortening at
least 30% by echocardiogram

- No congestive heart failure

- No uncontrolled cardiac arrhythmia

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum tolerated dose (MTD) assessed by Common Toxicity Criteria (CTC)

Outcome Time Frame:

28 days

Safety Issue:

Yes

Principal Investigator

Jon Wigginton

Investigator Role:

Principal Investigator

Investigator Affiliation:

New Approaches to Neuroblastoma Treatment (NANT)

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2009-00024

NCT ID:

NCT00054405

Start Date:

December 2002

Completion Date:

Related Keywords:

  • Recurrent Neuroblastoma
  • Neuroblastoma

Name

Location

Children's Hospital of PhiladelphiaPhiladelphia, Pennsylvania  19104
Children's Hospital Los AngelesLos Angeles, California  90027-0700
University of Wisconsin Hospital and ClinicsMadison, Wisconsin  53792-0001
Cincinnati Children's Hospital Medical CenterCincinnati, Ohio  45229-3039
Children's Hospital BostonBoston, Massachusetts  02115
Texas Children's HospitalHouston, Texas  
Seattle Children's HospitalSeattle, Washington  98105
Childrens Memorial HospitalChicago, Illinois  60614
University of Michigan University HospitalAnn Arbor, Michigan  48109
Riley Hospital for ChildrenIndianapolis, Indiana  46202
University of California at San Francisco - Comprehensive Cancer CenterSan Francisco, California  94143-0875
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, California  94304
New Approaches to Neuroblastoma Treatment (NANT)Los Angeles, California  90027-6016
AFLAC Cancer Center and Blood Disorders ServiceAtlanta, Georgia  30322