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

NCT01404702 | Terminated Phase 1 DMC

• 2 other identifiers: UAB 1051F101013003
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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

Keywords

Neuroblastoma; Pediatrics; Refractory; Immunotherapy; Biological therapy; Lymphocytes; Cancer; Bisphosphonate

Outcome Measures

Primary Outcomes (1)

• Evaluate the safety and toxicity of zoledronic acid and aldesleukin

  The NCI Common Terminology Criteria for AEs will be used for reporting \& identification of dose limiting toxicities. DLTs will include any grade 3 non-hematologic toxicity not included here: Gr 3 nausea \& vomiting \& diarrhea, Gr 3 fever, Gr 3 skin toxicity that remains stable \& tolerable, or improves with treatment within 24 hrs, Gr 3 neurotoxicity with subjective findings, Gr 4 hematologic toxicity, which improves to at least Gr 2 or baseline pre-therapy values within one week of completing IL2 infusion, Gr 3 performance that returns to 50 or higher before the start of the next therapy cycle.

  1.5 years

Secondary Outcomes (4)

• Evaluate the biologic function of autologous expanded/activated gamma delta T cells in neuroblastoma patients receiving therapy with zoledronic acid and aldesleukin

  3 years

• Evaluate immune phenotype of in vivo expanded/activated autologous gamma delta T cells

  3 years

• To document tumor response in patients with measurable disease.

  3 years

• Determine the ability of in vivo expanded/activated gamma delta T cells to infiltrate neuroblastoma tissue using immunohistochemical techniques when post-therapy specimens are available.

  3 years

Study Arms (1)

Zoledronic Acid and Interleukin-2

EXPERIMENTAL

Drug: Zoledronic Acid; Biological: Aldesleukin

Interventions

Zoledronic Acid DRUG

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

Also known as: Zometa

Zoledronic Acid and Interleukin-2

Aldesleukin 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

Also known as: Proleukin, Interleukin-2

Zoledronic Acid and Interleukin-2

Eligibility Criteria

• Age: 2 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• , 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham-Children's of Alabama

Birmingham, Alabama, 35233, United States

Location

MeSH Terms

Conditions

Neuroblastoma; Neoplasms

Interventions

Zoledronic Acid; aldesleukin; Interleukin-2

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Diphosphonates; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors

Study Officials

• Joseph Pressey, MD

  The University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 13, 2011
• First Posted: July 28, 2011
• Study Start: August 1, 2011
• Primary Completion: August 1, 2014
• Study Completion: August 1, 2014
• Last Updated: December 2, 2014

Record last verified: 2014-12

Locations

US (1)