Pilot Study of Zoledronic Acid and Interleukin-2 for Refractory Pediatric Neuroblastoma
This study has been terminated.
(Accrual slower than anticipated)
Information provided by (Responsible Party):
University of Alabama at Birmingham
First received: July 13, 2011
Last updated: December 1, 2014
Last verified: December 2014
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.
Drug: Zoledronic Acid
||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Pilot Study of Zoledronic Acid and Interleukin-2 for Refractory Pediatric Neuroblastoma: Assessment of Tolerability and In Vivo Expansion γδ T-Cells
Primary Outcome Measures:
- Evaluate the safety and toxicity of zoledronic acid and aldesleukin [ Time Frame: 1.5 years ] [ Designated as safety issue: Yes ]
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.
Secondary Outcome Measures:
- Evaluate the biologic function of autologous expanded/activated gamma delta T cells in neuroblastoma patients receiving therapy with zoledronic acid and aldesleukin [ Time Frame: 3 years ] [ Designated as safety issue: No ]
The ability of gamma-delta T cells derived from patients' peripheral blood to kill NB cells in vitro will be quantified by standard tumor cytotoxicity assays.
- Evaluate immune phenotype of in vivo expanded/activated autologous gamma delta T cells [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Peripheral blood mononuclear cells will be immunophenotyped by standard conjugation of fluorescent monoclonal antibodies in order to quantify and phenotype patient lymphocytes using flow cytometry.
- To document tumor response in patients with measurable disease. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Tumor response and progression will be assessed and documented utilizing the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
- 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. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
Patients with known or suspected bone marrow metastasis will undergo bilateral bone marrow biopsies at the beginning and end of the first course of therapy. This tissue will be fixed and processed per protocol (Appendix I) and infiltrating lymphocytes per hpf will be documented under standard microscopy.
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||August 2014 (Final data collection date for primary outcome measure)
Experimental: Zoledronic Acid and Interleukin-2
Drug: Zoledronic Acid
4 mg/m2/dose given iv on day 0 of every 28 day cycle
Other Name: Zometa
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
|Ages Eligible for Study:
||2 Years to 21 Years (Child, Adult)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01404702
|University of Alabama at Birmingham-Children's of Alabama
|Birmingham, Alabama, United States, 35233 |
University of Alabama at Birmingham
||Joseph Pressey, MD
||The University of Alabama at Birmingham
||University of Alabama at Birmingham
History of Changes
|Other Study ID Numbers:
|Study First Received:
||July 13, 2011
||December 1, 2014
||United States: Institutional Review Board
United States: Food and Drug Administration
Keywords provided by University of Alabama at Birmingham:
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on August 25, 2016
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Bone Density Conservation Agents
Physiological Effects of Drugs
Sensory System Agents
Peripheral Nervous System Agents