NeuroblastomaPhase 1NCT01404702
Pilot Study of Zoledronic Acid and Interleukin-2 for Refractory Pediatric Neuroblastoma
A Phase 1 study testing Zoledronic Acid and Aldesleukin in people with Neuroblastoma, run by University of Alabama at Birmingham at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Zoledronic Acid and Aldesleukin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2011to Aug 2014
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 21Show fewer
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham-Children's of Alabama
Birmingham, Alabama, 35233
About this study
Official title: Pilot Study of Zoledronic Acid and Interleukin-2 for Refractory Pediatric Neuroblastoma: Assessment of Tolerability and In Vivo Expansion γδ T-Cells
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
- Being tested
- Zoledronic Acid, Aldesleukin
- Keywords
- Neuroblastoma, Pediatrics, Refractory, Immunotherapy, Biological therapy, Lymphocytes, Cancer, Bisphosphonate
- Medical subject headings
- Neuroblastoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Zoledronic AcidDrug
Also called Zometa
4 mg/m2/dose given iv on day 0 of every 28 day cycle
AldesleukinBiological
Also called Proleukin, Interleukin-2
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
| Study group | Role | What they receive |
|---|---|---|
| Zoledronic Acid and Interleukin-2 | Experimental | Not described Receives: Drug: Zoledronic Acid; Biological: Aldesleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
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.
Measured: 3 years
Evaluate immune phenotype of in vivo expanded/activated autologous gamma delta T cells
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.
Measured: 3 years
To document tumor response in patients with measurable disease.
Tumor response and progression will be assessed and documented utilizing the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Measured: 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.
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.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2011 (estimated)
- Study startAug 2011
- Primary completionAug 2014
- Study completionAug 2014
Why it stopped: Accrual slower than anticipated
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Joseph Pressey, MD, Principal investigator, The University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01404702
- Sponsor's protocol ID
- UAB 1051
- Other IDs
- F101013003
- Status last verified
- Dec 2014
- First submitted
- 13 Jul 2011
- Last updated
- 2 Dec 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Zoledronic Acid and Interleukin-2 for Refractory Pediatric Neuroblastoma: Assessment of Tolerability and In Vivo Expansion γδ T-Cells
- ClinicalTrials.gov ID
- NCT01404702
- Acronym / sponsor ID
- UAB 1051
- Conditions
- Neuroblastoma
- Keywords
- Neuroblastoma, Pediatrics, Refractory, Immunotherapy, Biological therapy, Lymphocytes, Cancer, Bisphosphonate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Accrual slower than anticipated
- Enrolment
- 4 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Study start
- Aug 2011
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 28 Jul 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Zoledronic Acid and Interleukin-2 | Experimental | Drug: Zoledronic Acid, Biological: Aldesleukin |
Who may qualify
- Ages
- 2 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (21 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Zoledronic AcidAlso: Zometa4 mg/m2/dose given iv on day 0 of every 28 day cycle | Drug | Zoledronic Acid and Interleukin-2 |
| AldesleukinAlso: Proleukin, Interleukin-2Dose 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 | Biological | Zoledronic Acid and Interleukin-2 |
Primary outcome
Evaluate the safety and toxicity of zoledronic acid and aldesleukin
Time frame: 1.5 years
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.
4 secondary outcomes
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
Evaluate immune phenotype of in vivo expanded/activated autologous gamma delta T cells
Time frame: 3 years
To document tumor response in patients with measurable disease.
Time frame: 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.
Time frame: 3 years
Results and safety
The study was stopped early (reason given: Accrual slower than anticipated). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joseph Pressey, MD principal investigator
The University of Alabama at Birmingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Zoledronic Acid and Aldesleukin in people with Neuroblastoma, run by University of Alabama at Birmingham at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 2 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Accrual slower than anticipated). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety and toxicity of zoledronic acid and aldesleukin (time frame: 1.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2014.