Pilot Study of Zoledronic Acid and Interleukin-2 for Refractory Pediatric Neuroblastoma

NCT ID: NCT01404702

Last Updated: 2014-12-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31
• Study Completion Date: 2014-08-31

Brief Summary

Neuroblastoma (NB) is the most common extracranial solid tumor in children, with an annual incidence of 10.5 per million children less than 15 years of age. NB accounts for 15% of childhood cancer deaths. High risk (HR) patients carry a poor prognosis despite treatment with intensive chemotherapy, surgery and/or radiation, autologous bone marrow transplant, and treatment with cis-retinoic acid. New therapies are desperately needed for such patients. Recently, it has been demonstrated that HR NB patients benefit from anti-GD2 antibody therapy which directs the immune system against NB cells. To further explore means of harnessing the immune system to attack NB, the investigators are studying the combination of zoledronic acid (ZOL) and interleukin-2 (IL-2). ZOL has been demonstrated to have direct anti-neuroblastoma effects in laboratory studies. ZOL also augments the production of tumor killing white blood cells called gamma-delta T cells. When used in combination with IL-2, ZOL is capable of eliciting potent anti-cancer effects in patients, in part, via the expansion of gamma-delta T cells. In this present trial the investigators aim to study the tolerability of the combination of ZOL and IL-2 in pediatric NB patients. Patients will also be monitored radiologically for tumor response to therapy. Correlative biological studies will study the ability of this drug combination to elicit the production of NB killing gamma-delta T cells in children.

Conditions

Neuroblastoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Zoledronic Acid and Interleukin-2

Group Type: EXPERIMENTAL

Zoledronic Acid

Intervention Type: DRUG

4 mg/m2/dose given iv on day 0 of every 28 day cycle

Aldesleukin

Intervention Type: BIOLOGICAL

Dose Level 1: 3 x 10^6 IU/m2/day given subcutaneously on days 0 through 4 and 14 through 18 every 28 day cycle

Dose Level 2: 6 x 10^6 IU/m2/day given subcutaneously on days 0 through 4 and 14 through 18 every 28 day cycle

Interventions

Zoledronic Acid

4 mg/m2/dose given iv on day 0 of every 28 day cycle

Intervention Type: DRUG

Aldesleukin

Dose Level 1: 3 x 10^6 IU/m2/day given subcutaneously on days 0 through 4 and 14 through 18 every 28 day cycle

Dose Level 2: 6 x 10^6 IU/m2/day given subcutaneously on days 0 through 4 and 14 through 18 every 28 day cycle

Intervention Type: BIOLOGICAL

Other Intervention Names

Zometa; Proleukin; Interleukin-2

Eligibility Criteria

Inclusion Criteria

• All patients must be diagnosed with treatment-refractory neuroblastoma with no known curative treatment options. Tumor histology should be verified at diagnosis or relapse.
• Prior to enrollment, a determination of residual disease must be performed
• Patients must have a Lansky or Karnofsky performance scale score of ≥ 50%.
• Patients must have a life expectancy of ≥ 2 months (8 weeks).
• Total absolute neutrophil count (ANC) is at least 750, Hgb≥8 grams/dl, and plts ≥ 75K. PRBC transfusions are allowed.
• Patients with bone marrow disease will not evaluable for hematologic toxicity. These patients must have a peripheral absolute neutrophil count

• 750, platelet count ≥ 50K and Hgb ≥8 grams/dl. Transfusions are permitted to meet both the platelet and hemoglobin criteria.
• Creatinine clearance or radioisotope GFR > 70mL/min/1.73 m2 or a serum creatinine based on age/gender as follows:
• ≤ 0.8 mg/dL (for patients 2 to 5 years of age)
• ≤ 1.0 mg/dL (for patients 6 to 9 years of age)
• ≤ 1.2 mg/dL (for patients 10 to 12 years of age)
• ≤ 1.4 mg/dL (for female patients ≥ 13 years of age)
• ≤ 1.5 mg/dL (for male patients 13 to 15 years of age)
• ≤ 1.6 mg/dL (for male patients ≥ 16 years of age)
• Total bilirubin ≤ 2.5 x upper limit of normal (ULN) for age, and
• SGPT (ALT) < 2.5 x upper limit of normal (ULN) for age.
• SOS (sinusoidal obstruction syndrome, formerly known as veno-occlusive disease [VOD]), if present, should be stable or improving.
• Shortening fraction of > 27% by echocardiogram, or ejection fraction of > 55% by radionuclide angiography.
• No evidence of dyspnea at rest. If PFTs are performed, FEV1/FVC > 60% by pulmonary function test.
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled.
• CNS toxicity < Grade 2.

Exclusion Criteria

• Females of childbearing potential must have a negative pregnancy test.
• Patients of childbearing potential must agree to use an effective birth control method.
• Female patients who are lactating must agree to stop breast-feeding.
• All patients and/or their parents or legal guardians must sign a written informed consent.
• All institutional requirements for human studies must be met.
• Previous treatment with anti-GD2 and interleukin2 therapy

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 21 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Alabama at Birmingham

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Joseph Pressey, MD

Role: PRINCIPAL_INVESTIGATOR

The University of Alabama at Birmingham

Locations

University of Alabama at Birmingham-Children's of Alabama

Birmingham, Alabama, United States

Countries

United States

Other Identifiers

F101013003

Identifier Type: OTHER

Identifier Source: secondary_id

UAB 1051

Identifier Type: -

Identifier Source: org_study_id