NeuroblastomaPhase 1NCT01576692
Combination Chemotherapy, Monoclonal Antibody, and Natural Killer Cells in Treating Young Patients With Recurrent or Refractory Neuroblastoma
A Phase 1 study testing Humanized anti-GD2 antibody, Chemotherapy and Cytokines in people with Neuroblastoma, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
This is a safety / feasibility trial evaluating the combination of a humanized anti-GD2 antibody (HU14.18K322A) manufactured at the Children's GMP, LLC at St. Jude with allogeneic natural killer (NK) cells and standard chemotherapy in children with relapsed or refractory neuroblastoma. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Humanized anti-GD2 antibody, Chemotherapy and Cytokines
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2012to 17 Oct 2018
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of recurrent or refractory neuroblastoma.
- Age < 22 years at the time of enrollment.
- Measurable or evaluable (detectable by bone scan or MIBG, but not measurable) disease.
- Organ function: Must have adequate organ and marrow function as defined by the following parameters:
- Bone marrow: Absolute neutrophil count (ANC) > 750/mm3; Platelets > 75,000/mm3 (no platelet transfusions for at least 1 week)
- Hepatic: Total bilirubin ≤ 2 x upper limit of normal (ULN) for age; SGPT (ALT) ≤ 2.5 x ULN for age.
Show all 27Show fewer
- Renal: Creatinine clearance or radioisotope GFR equal to or >70 ml/min/1.73m2 OR serum creatinine based on age as follows:
- Age 5 years of age and under, then maximum serum creatinine 0.8 mg/dL
- Age >5 and equal to or <10 years, then maximum serum creatinine 1.0 mg/dL
- Age >10 and equal to or <15 years, then maximum serum creatinine 1.2 mg/dL
- Age >15 years, then maximum serum creatinine 1.5 mg/dL
- Cardiovascular: Shortening fraction > or equal to 27% by echocardiogram; Corrected QT interval < or equal to 450 milliseconds
- Performance status: Karnofsky > or equal to 50 for > 10 years of age; Lansky > or equal to 50 for children equal to or < 10 years of age.
- Prior therapy: Participant must have fully recovered from the acute toxic effects of all prior therapy prior to enrolling on study.
- Myelosuppressive chemotherapy: Must not have received myelosuppressive therapy within 2 weeks prior to study entry (4 weeks if nitrosurea).
- Biologic (anti-neoplastic agent): At least 7 days since the completion of therapy with biologic agent, including retinoic acid. At least 6 weeks must have elapsed since prior therapy that includes a monoclonal antibody. Participants receiving IVIG are eligible; however, participant must not receive IVIG during the 4 days of antibody infusion.
- Radiation therapy: At least 2 weeks since prior local radiation therapy at the time of study entry.
- Growth factors: Must not have received hematopoietic growth factors (G-CSF, GM-CSF) for at least 1 week prior to study entry.
- Investigational agent: Must not have received investigational agent within 7 days of study entry.
- Immune therapy: Must not have received immunosuppressive (including glucocorticoids), immunostimulatory or any immunomodulatory treatment within 2 weeks of study entry. Steroid containing inhalers, steroid replacement for adrenal insufficiency and steroid premedication for prevention of transfusion or imaging contrast-agent related allergic reaction will be permitted.
- Participants may have had prior CNS metastasis providing: CNS disease has been previously treated and CNS disease has been clinically stable for 4 weeks prior to study entry (assessment must be made by CT or MRI).
- Written informed consent following institutional and federal guidelines.
- Donor is a partially matched family member.
- Donor is HIV negative.
- Donor is at least 18 years of age.
- Donor is not pregnant.
- Donor does not have any other medical condition that, in the opinion of an independent physician, precludes performance of an apheresis procedure.
Who cannot join
- Prior monoclonal antibody: Participants having received in vivo monoclonal anti-GD2 antibodies for biologic therapy or for tumor imaging are ineligible if they have experienced a severe allergic reaction while receiving prior anti-GD2 therapy.
- Pregnancy or breast feeding: Study participants who are pregnant are not eligible for this study. Pregnancy tests must be obtained in girls who are > 10 years of age or post-menarchal within 7 days prior to study enrollment. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during participation in the trial. Breast feeding should be discontinued if a mother wishes to participate in this study.
- Allergy: Known hypersensitivity to other recombinant human antibodies.
- An uncontrolled infection.
- Participants who have not started protocol therapy within 7 days of study enrollment.
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: A Safety/Feasibility Trial of the Addition of the Humanized Anti-GD2 Antibody (hu14.18K322A) With and Without Natural Killer Cells to Chemotherapy in Children and Adolescents With Recurrent/Refractory Neuroblastoma
This is a safety / feasibility trial evaluating the combination of a humanized anti-GD2 antibody (HU14.18K322A) manufactured at the Children's GMP, LLC at St. Jude with allogeneic natural killer (NK) cells and standard chemotherapy in children with relapsed or refractory neuroblastoma.
Read the detailed description
Eligible participants will receive chemotherapy combined with Hu14.18K322A antibody daily for four consecutive days. Those participants who go on to receive the second course of chemotherapy with Hu14.18K322A will receive an infusion of allogeneic NK cells after the 4th dose of Hu14.18K322A antibody. A maximum of six courses will be given.
Primary Objective:
- To observe and describe the toxicities associated with humanized anti-GD2 antibody (hu14.18K322A) with and without allogeneic NK cells when given with repeated cycles of chemotherapy to children with refractory/relapsed neuroblastoma.
Secondary Objective:
- To describe response, time to progression, event-free and overall survival.
- To evaluate the feasibility of administering NK cells from a suitable donor after completion of the last dose of hu14.18K322A in three repeated cycles of chemotherapy
- Conditions
- Neuroblastoma
- Being tested
- Humanized anti-GD2 antibody, Chemotherapy, Cytokines, Natural killer cells, CliniMACS
- Keywords
- recurrent neuroblastoma, refractory neuroblastoma, natural killer cells
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Humanized anti-GD2 antibodyBiological
Also called Hu14.18K322A monoclonal antibody
A maximum of 6 courses of therapy may be given on the following schedule:
- Courses 1, 3, and 5: Humanized anti-GD2 antibody + chemotherapy
- Courses 2, 4, and 6: Humanized anti-GD2 antibody + chemotherapy, with or without natural killer (NK) cells (depending on availability of appropriate NK donor)
- Humanized anti-GD2 antibody (hu14.18 K322A) dosage: 40 mg/m^2)/dose, over 4 hours daily
- NK Cell dosage: minimum of 0.1 * 10^6 cells/kg; maximum of 400 * 10^6 CD45+ cells/kg, given once
ChemotherapyDrug
Also called Cytoxan, Hycamtin, Temodar, Camptosar
Chemotherapy may include the following at the dosages shown below:
- cyclophosphamide: 400 mg/m^2 IV days 1-5
- topotecan: 1.2 mg/m^2 IV days 1-5
- temozolomide: 150 mg/m^2 PO at least 1 hour before irinotecan
- irinotecan: 50 mg/m^2 IV over 1 hour daily for 5 days
- carboplatin (AUC 8-dosing based on GFR), IV day 1 only
- ifosfamide: 2 g/m2 IV days 1-3
- etoposide: 100 mg/m2 days 1-3
CytokinesOther
Also called IL-2, Aldesleukin, Proleukin, Sargramostim
Cytokines may be given at the following dosages:
- interleukin-2: 1 million units/m^2 SQ beginning day 6 of each chemotherapy course and continued every other day for 6 doses
- GM-CSF: 250 mcg/m^2/day beginning on day 7 or day 8 of chemotherapy course and continued daily through the nadir until ANC >2,000/mm^3
Natural killer cellsBiological
Also called NK cells
NK cells from haploidentical family donor will be infused on day 7 or 8, depending on course. NK cells may be infused in either the inpatient or outpatient setting by a physician, Physician Assistant, Nurse Practitioner, or qualified RN. Careful monitoring and supportive care during NK cell infusion will be guided in part by the Standard Operating Procedures for Lymphocytes Infusions in the St. Jude Nursing Policy \& Procedure Manual.
CliniMACSDevice
Also called Cell Selection System
The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Participants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells.
Cells for infusion are prepared using the CliniMACS System. Receives: Biological: Humanized anti-GD2 antibody; Drug: Chemotherapy; Other: Cytokines; Biological: Natural killer cells; Device: CliniMACS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients experiencing unacceptable toxicity associated with humanized anti-GD2 antibody/chemotherapy (course 1) and anti-GD2 antibody/chemotherapy/NK cells (course 2).
Unacceptable toxicities are defined as: 1) any grade 4 toxicity that does not return to baseline by day 35, 2) any toxicity requiring the use of pressors, including grade 4 acute capillary leak syndrome or grade 3 or 4 hypotension, 3) any toxicity requiring ventilation support, including grade 4 respiratory toxicity, 4) grade 4 neutropenia or thrombocytopenia lasting > 35 days (only during course 2), and 5) death from toxicity.
Measured: First two courses of treatment (42 days)
Secondary outcomes (4)
Response to treatment
Clinical outcome measured as response to therapy using the RECIST response evaluation criteria in solid tumors and/or clearing of bone marrow and/or improvement in MIBG scans.
Measured: Baseline and three (3) weeks following courses 2, 4, and 6
Time to progression.
Measured: Time from date of study enrollment to date of disease progression or recurrence, assessed up to 4.5 years.
Event free survival.
Event-free survival will be estimated using the method of Kaplan and Meier.
Measured: Time from date of study enrollment to date of first event (relapsed or progressive disease, second malignancy or death from any cause) or to the date of last contact for patients without events, assessed up to 4.5 years.
Overall survival
Survival will be estimated using the method of Kaplan and Meier.
Measured: Time from date of study enrollment to date of death from any cause or to the date of last contact for survivors, assessed up to 4.5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Apr 2012 (estimated)
- Study startApr 2012
- Primary completionOct 2014
- Study completion17 Oct 2018
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 St. Jude Children's Research HospitalThe 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
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- CURE Childhood Cancer, Inc.
- Responsible party
- Sponsor
- Investigators
- Wayne L. Furman, MD, Principal investigator, St. Jude Children's Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01576692
- Sponsor's protocol ID
- GD2NK
- Other IDs
- NCI-2012-00495
- Status last verified
- Nov 2018
- First submitted
- 10 Apr 2012
- Last updated
- 15 Nov 2018
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety/Feasibility Trial of the Addition of the Humanized Anti-GD2 Antibody (hu14.18K322A) With and Without Natural Killer Cells to Chemotherapy in Children and Adolescents With Recurrent/Refractory Neuroblastoma
- ClinicalTrials.gov ID
- NCT01576692
- Acronym / sponsor ID
- GD2NK
- Conditions
- Neuroblastoma
- Keywords
- recurrent neuroblastoma, refractory neuroblastoma, natural killer cells
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- CURE Childhood Cancer, Inc.
- Study start
- Apr 2012
- Primary completion
- Oct 2014 (actual)
- Study completion
- 17 Oct 2018 (actual)
- First posted
- 12 Apr 2012 (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.
This is a safety / feasibility trial evaluating the combination of a humanized anti-GD2 antibody (HU14.18K322A) manufactured at the Children's GMP, LLC at St. Jude with allogeneic natural killer (NK) cells and standard chemotherapy in children with relapsed or refractory neuroblastoma.
Detailed description
Eligible participants will receive chemotherapy combined with Hu14.18K322A antibody daily for four consecutive days. Those participants who go on to receive the second course of chemotherapy with Hu14.18K322A will receive an infusion of allogeneic NK cells after the 4th dose of Hu14.18K322A antibody. A maximum of six courses will be given.
Primary Objective:
- To observe and describe the toxicities associated with humanized anti-GD2 antibody (hu14.18K322A) with and without allogeneic NK cells when given with repeated cycles of chemotherapy to children with refractory/relapsed neuroblastoma.
Secondary Objective:
- To describe response, time to progression, event-free and overall survival.
- To evaluate the feasibility of administering NK cells from a suitable donor after completion of the last dose of hu14.18K322A in three repeated cycles of chemotherapy
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Biological: Humanized anti-GD2 antibody, Drug: Chemotherapy, Other: Cytokines, Biological: Natural killer cells, Device: CliniMACSParticipants receive humanized anti-GD2 antibody, chemotherapy, cytokines, and natural killer cells. Cells for infusion are prepared using the CliniMACS System. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (27 listed)
- Diagnosis of recurrent or refractory neuroblastoma.
- Age < 22 years at the time of enrollment.
- Measurable or evaluable (detectable by bone scan or MIBG, but not measurable) disease.
- Organ function: Must have adequate organ and marrow function as defined by the following parameters:
- Performance status: Karnofsky > or equal to 50 for > 10 years of age; Lansky > or equal to 50 for children equal to or < 10 years of age.
Key exclusion criteria (5 listed)
- Prior monoclonal antibody: Participants having received in vivo monoclonal anti-GD2 antibodies for biologic therapy or for tumor imaging are ineligible if they have experienced a severe allergic reaction while receiving prior anti-GD2 therapy.
- Pregnancy or breast feeding: Study participants who are pregnant are not eligible for this study. Pregnancy tests must be obtained in girls who are > 10 years of age or post-menarchal within 7 days prior to study enrollment. Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method during participation in the trial. Breast feeding should be discontinued if a mother wishes to participate in this study.
- Allergy: Known hypersensitivity to other recombinant human antibodies.
- An uncontrolled infection.
- Participants who have not started protocol therapy within 7 days of study enrollment.
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 |
|---|---|---|
| Humanized anti-GD2 antibodyAlso: Hu14.18K322A monoclonal antibodyA maximum of 6 courses of therapy may be given on the following schedule: * Courses 1, 3, and 5: Humanized anti-GD2 antibody + chemotherapy * Courses 2, 4, and 6: Humanized anti-GD2 antibody + chemotherapy, with or without natural killer (NK) cells (depending on availability of appropriate NK donor) * Humanized anti-GD2 antibody (hu14.18 K322A) dosage: 40 mg/m^2)/dose, over 4 hours daily * NK Cell dosage: minimum of 0.1 * 10^6 cells/kg; maximum of 400 * 10^6 CD45+ cells/kg, given once | Biological | Treatment |
| ChemotherapyAlso: Cytoxan, Hycamtin, Temodar, CamptosarChemotherapy may include the following at the dosages shown below: * cyclophosphamide: 400 mg/m^2 IV days 1-5 * topotecan: 1.2 mg/m^2 IV days 1-5 * temozolomide: 150 mg/m^2 PO at least 1 hour before irinotecan * irinotecan: 50 mg/m^2 IV over 1 hour daily for 5 days * carboplatin (AUC 8-dosing based on GFR), IV day 1 only * ifosfamide: 2 g/m2 IV days 1-3 * etoposide: 100 mg/m2 days 1-3 | Drug | Treatment |
| CytokinesAlso: IL-2, Aldesleukin, Proleukin, SargramostimCytokines may be given at the following dosages: * interleukin-2: 1 million units/m^2 SQ beginning day 6 of each chemotherapy course and continued every other day for 6 doses * GM-CSF: 250 mcg/m^2/day beginning on day 7 or day 8 of chemotherapy course and continued daily through the nadir until ANC >2,000/mm^3 | Other | Treatment |
| Natural killer cellsAlso: NK cellsNK cells from haploidentical family donor will be infused on day 7 or 8, depending on course. NK cells may be infused in either the inpatient or outpatient setting by a physician, Physician Assistant, Nurse Practitioner, or qualified RN. Careful monitoring and supportive care during NK cell infusion will be guided in part by the Standard Operating Procedures for Lymphocytes Infusions in the St. Jude Nursing Policy \& Procedure Manual. | Biological | Treatment |
| CliniMACSAlso: Cell Selection SystemThe mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells. | Device | Treatment |
Primary outcome
Number of patients experiencing unacceptable toxicity associated with humanized anti-GD2 antibody/chemotherapy (course 1) and anti-GD2 antibody/chemotherapy/NK cells (course 2).
Time frame: First two courses of treatment (42 days)
Unacceptable toxicities are defined as: 1) any grade 4 toxicity that does not return to baseline by day 35, 2) any toxicity requiring the use of pressors, including grade 4 acute capillary leak syndrome or grade 3 or 4 hypotension, 3) any toxicity requiring ventilation support, including grade 4 respiratory toxicity, 4) grade 4 neutropenia or thrombocytopenia lasting > 35 days (only during course 2), and 5) death from toxicity.
4 secondary outcomes
Response to treatment
Time frame: Baseline and three (3) weeks following courses 2, 4, and 6
Time to progression.
Time frame: Time from date of study enrollment to date of disease progression or recurrence, assessed up to 4.5 years.
Event free survival.
Time frame: Time from date of study enrollment to date of first event (relapsed or progressive disease, second malignancy or death from any cause) or to the date of last contact for patients without events, assessed up to 4.5 years.
Overall survival
Time frame: Time from date of study enrollment to date of death from any cause or to the date of last contact for survivors, assessed up to 4.5 years.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2018.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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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.
Wayne L. Furman, MD principal investigator
St. Jude Children's Research Hospital
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 Humanized anti-GD2 antibody, Chemotherapy and Cytokines in people with Neuroblastoma, run by St. Jude Children's Research Hospital 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 27 inclusion and 5 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: finished, as of the sponsor's last update on 15 Nov 2018. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Number of patients experiencing unacceptable toxicity associated with humanized anti-GD2 antibody/chemotherapy (course 1) and anti-GD2 antibody/chemotherapy/NK cells (course 2). (time frame: First two courses of treatment (42 days)). 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 15 Nov 2018.