AzTrials
AzTrials

NeuroblastomaPhase 2NCT01857934

Therapy for Children With Advanced Stage Neuroblastoma

A Phase 2 study testing cyclophosphamide, topotecan and hu14.18K322A in people with Neuroblastoma, run by St. Jude Children's Research Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Neuroblastoma is the most common extracranial solid tumor in childhood, with nearly 50% of patients presenting with widespread metastatic disease. The current treatment for this group of high-risk patients includes intensive multi-agent chemotherapy (induction) followed by myeloablative therapy with stem-cell rescue… Read more about this study

Who is it for?
Ages Up to 18 years
Conditions the study is for
Neuroblastoma
What is being tested?
cyclophosphamide, topotecan and hu14.18K322A
Could I receive a placebo?
No, everyone receives an active treatment
How many people
153 participants
Where
1 siteUnited States
Study dates
5 Jul 2013to 31 Dec 2025
Phase
Phase 2

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 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

PARTICIPANT Inclusion Criteria:

  • Participants <19 years of age (eligible until 19th birthday).
  • Newly diagnosed, advanced stage, high-risk neuroblastoma defined as one of the following:
  • Children < 1 year with International Neuroblastoma Staging System (INSS) stage 2a, 2b, 3, 4 or 4S disease AND MYCN amplification (>10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal).
  • INSS 2a or 2b disease AND MYCN amplification, regardless of age or additional biologic features
  • INSS stage 3 AND:
  1. MYCN amplification (>10 copies, or greater than four-fold increase in MYCN signal as compared to reference signal, regardless of age or additional biologic features
  2. Age > 18 months (> 547 days) with unfavorable pathology, regardless of MYCN status
  • INSS stage 4 and:
  1. MYCN amplification, regardless of age or additional biologic features
  2. Age > 18 months (> 547 days) regardless of biologic features
  3. Age 12 - 18 months (365 - 547 days) with any of the following three unfavorable biologic features (MYCN amplification, unfavorable pathology and/or DNA index =1) or any biologic feature that is indeterminant/unknown
  • Children at least 365 days initially diagnosed with: INSS stage 1, 2, 4S who progressed to a stage 4 without interval chemotherapy.
  • Histologic proof of neuroblastoma or positive bone marrow for tumor cells with increased urine catecholamines.
  • Adequate renal and hepatic function (serum creatinine <3 x upper limit of normal for age, AST< 3 x upper limit of normal).
  • No prior therapy, unless an emergency situation requires local tumor treatment (discuss with principal investigator).
  • Written, informed consent according to institutional guidelines.

PARTICIPANT Exclusion Criteria:

  • Any evidence, as judged by the investigator, of severe or uncontrolled systemic disease (e.g., unstable or uncompensated respiratory, cardiac, hepatic, or renal disease).
  • Pregnant or breast feeding (female of child-bearing potential).
  • Children with INSS 4 disease, age <18 months with all 3 favorable biologic features (non-amplified MYCN, favorable pathology and DNA index >1).

DONOR Inclusion Criteria:

  • Potential donor is a biologic parent
  • Potential donor is at least 18 years of age.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105

Other trials in United States

About this study

Official title: Neuroblastoma Protocol 2012: Therapy for Children With Advanced Stage High-Risk Neuroblastoma

Neuroblastoma is the most common extracranial solid tumor in childhood, with nearly 50% of patients presenting with widespread metastatic disease. The current treatment for this group of high-risk patients includes intensive multi-agent chemotherapy (induction) followed by myeloablative therapy with stem-cell rescue (consolidation) and then treatment of minimal residual disease (MRD) with isotretinoin. Recently a new standard of care was established by enhancing the treatment of MRD with the addition of a monoclonal antibody (ch14.18) which targets a tumor-associated antigen, the disialoganglioside GD2, which is uniformly expressed by neuroblasts. Despite improvement in 2-year event-free survival (EFS) of 20%, more than one-third of children with high-risk neuroblastoma (HR defined in) still cannot be cured by this approach. Therefore, novel therapeutic approaches are needed for this subset of patients. This study will be a pilot Phase II study of a unique anti-disialoganglioside (anti-GD2) monoclonal antibody (mAb) called hu14.18K322A, given with induction chemotherapy.

PRIMARY OBJECTIVE:

Read more
  • To study the efficacy [response: complete remission + partial remission (CR+PR)] to two initial courses of cyclophosphamide and topotecan combined with hu14.18K322A (4 doses/course followed by GM-CSF) in previously untreated children with high-risk neuroblastoma.
  • To estimate the event-free survival of patients with newly diagnosed high-risk neuroblastoma treated with the addition of hu14.18K322A to treatment.

SECONDARY OBJECTIVES:

  • To study the feasibility of delivering hu14.18K322A to 6 cycles induction chemotherapy and describe the antitumor activity (CR+PR) of this 6 course induction therapy.
  • To estimate local control and pattern of failure associated with focal intensity modulated or proton beam radiation therapy dose delivery in high-risk abdominal neuroblastoma.
  • To describe the tolerability of four doses of hu14.18K322A with allogeneic natural killer (NK) cells from an acceptable parent, in the immediate post-transplant period [day +2 - +5 after peripheral blood stem cell (PBSC) infusion] in consenting participants.
  • To describe the tolerability of hu14.18K322A with interleukin-2 and GM-CSF as treatment for minimal residual disease (MRD).
Read the detailed description

The phases of the study are:

  1. Screening phase: Tests and evaluations will be done before treatment starts.
  2. Induction phase: Includes chemotherapy plus hu14.18K322A mAb. Participants will also have surgery during this part of the study to remove as much tumor as possible.
  3. Consolidation/Intensification phase: Includes high doses of chemotherapy and blood stem cell transplantation with additional, experimental "minimal residual disease" (MRD) treatment. Participants will also get radiation treatment to all sites of the tumor(s) after recovery from the stem cell transplant.
  4. Maintenance/MRD treatment phase: With immune therapy in addition to the standard treatment with the drug isotretinoin.
Conditions
Neuroblastoma
Being tested
cyclophosphamide, topotecan, hu14.18K322A, peripheral blood stem cell harvest, surgical resection
Keywords
Anti-GD2 monoclonal antibody, hu14.18K322A, High-risk neuroblastoma, Phase II, Allogeneic NK cells
Medical subject headings
Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • cyclophosphamideDrug

    Also called Cytoxan(R)

    Given intravenously (IV)

  • topotecanDrug

    Also called Hycamtin(R)

    Given IV

  • hu14.18K322ABiological

    Also called humanized anti-GD2 antibody, monoclonal antibody, dinutuximab

    Given IV

  • peripheral blood stem cell harvestProcedure or surgery

    Also called PBSCH

    Following evaluation and approval by a member of the transplant staff and completion of the consent form by the participant, collection of peripheral blood stem cells (PBSC) may take place.

  • surgical resectionProcedure or surgery

    The primary tumor will be resected surgically following two initial courses of chemotherapy, if feasible. Patients who are unable to have their primary tumor resected after the initial two courses of induction chemotherapy will undergo surgery for resection of the primary tumor mass and careful lymph node staging.

  • cisplatinDrug

    Also called Platinol-AQ(R)

    Given IV

  • etoposideDrug

    Also called VP16, Vepesid(R), Etopophos(R)

    Given IV

  • doxorubicinDrug

    Also called Adriamycin(R)

    Given IV

  • vincristineDrug

    Also called Oncovin(R)

    Given IV

  • busulfanDrug

    Also called Busulfex(R)

    Given IV

  • melphalanDrug

    Also called L-phenylalanine mustard, Phenylalanine mustard, L-PAM, L-sarcolysin

    Given IV

  • peripheral blood stem cell transplantationBiological

    Also called PBSCT

    Transplantation of previously harvested peripheral blood stem cells.

  • natural killer cell infusionBiological

    Also called NK cell infusion

    Natural killer (NK) cells obtained from a suitable donor will be given together with hu14.18K322A prior to early hematopoietic cell recovery. In the event there is not a suitable parental donor, consenting participants will receive an additional course of hu14.18K322A.

  • radiation therapyRadiation

    Radiation therapy to the primary and metastatic disease sites will follow peripheral blood stem cell transplant with the exception of any patient requiring emergent radiotherapy. External beam radiotherapy will be delivered to the primary site and select metastatic and bulky nodal sites.

  • GM-CSFBiological

    Also called sargramostim, Leukine(R), granulocyte macrophage colony stimulating factor

    Given subcutaneously (SQ)

  • G-CSFBiological

    Also called Granulocyte colony stimulating factor, Neupogen(R), Filgrastim

    Given subcutaneously (SQ)

  • mesnaDrug

    Also called Mesnex(R)

    Given IV

  • levetiracetamDrug

    Also called Keppra

    Given IV

  • interleukin-2Biological

    Also called IL-2, aldesleukin, Proleukin(R)

    Given by continuous infusion during MRD maintenance, and SQ during induction.

  • IsotretinoinDrug

    Also called 13-cis retinoic acid

    Given orally (PO)

  • 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 groups in NCT01857934
Study groupRoleWhat they receive
TreatmentExperimentalParticipants receive IV hu14.18K322A with each course of chemotherapy (cyclophosphamide, topotecan, cyclophosphamide, doxorubicin, vincristine, cisplatin, and etoposide). Mesna will be given prior to and after cyclophosphamide infusion. Peripheral blood stem cell harvest (PBSC) and surgical resection of primary tumor will be performed, if feasible. Intensification therapy includes busulfan, melphalan, and levetiracetam with peripheral blood stem cell transplantation. A course of hu14.18K322A with natural killer cell infusion will be given to consenting participants. Radiation therapy will follow PBSC transplant with the exception of any patient requiring emergent radiotherapy. MRD treatment includes hu14.18K322A, G-CSF, GM-CSF, interleukin-2 and isotretinoin. Cells for infusion are prepared using the CliniMACS System.
Receives: Drug: cyclophosphamide; Drug: topotecan; Biological: hu14.18K322A; Procedure: peripheral blood stem cell harvest; Procedure: surgical resection; Drug: cisplatin; Drug: etoposide; Drug: doxorubicin; Drug: vincristine; Drug: busulfan; Drug: melphalan; Biological: peripheral blood stem cell transplantation; Biological: natural killer cell infusion; Radiation: radiation therapy; Biological: GM-CSF; Biological: G-CSF; Drug: mesna; Drug: levetiracetam; Biological: interleukin-2; Drug: Isotretinoin; Device: CliniMACS

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall Response Rate [Complete Response + Very Good Partial Response + Partial Response (CR + VGPR + PR)]

    Per the 1993 INRC: measurable tumor defined as product of the longest x widest perpendicular diameter, elevated catecholamine levels and tumor cels in bone marrow. Complete Response (CR)-no evidence of primary tumor or metastases. Very Good Partial Response (VGPR)->90% reduction of primary tumor; no metastases; no new bone lesions, all pre-existing lesions improved. Partial Response (PR)-50-90% reduction of primary tumor; >50% reduction in measurable sites of metastases; 0-1 bone marrow samples with tumor; number of positive bone sites decreased by >50%. Mixed Response (MR)->50% reduction of any measurable lesion with <50% reduction in other sites; no new lesions; <25% increase in any existing lesion. No Response (NR)-no new lesions; <50% reduction but <25% increase in an any existing lesion. No Response (NR)-no new lesions; <50% reduction but <25% increase in any existing legions. Progressive Disease (PD)-any new/increased measurable lesion by >25%; previous negative marrow positive.

    Measured: After two initial courses of chemotherapy (approximately 6 weeks after enrollment)

  2. Event-free Survival (EFS)

    EFS was estimated as time to relapse, progressive disease, secondary neoplasm, or death from any cause from enrollment. The EFS was estimated by Kaplan-Meier method

    Measured: 3 years, from time of enrollment

Secondary outcomes (4)

  1. Feasibility of Delivering hu14.18K322A to 6 Cycles of Induction Therapy

    The study is designed to monitor the feasibility of delivering hu14.18K332A to 6 cycles of Induction chemotherapy. The feasibility of Induction therapy for this study will be to target no worse than 75%. A patient was considered as a "failure" for the 6 cycles of Induction therapy if the patient failed to complete Induction therapy within 155 days since treatment initiation due to toxicity or disease progression, unless the delay was a result of non-medical issues (e.g. not due to protocol toxicity). The proportion of patients who successfully received hu14.18K322A with 6 cycles of induction chemotherapy was estimated together with a 95% confidence interval. The response rate (CR + VGPR + PR) to 6 cycles of Induction chemoimmunotherapy was estimated together with the 95% confidence intervals

    Measured: After 6 cycles of induction therapy (approximately 24 weeks after enrollment)

  2. Local Failure Rate and Pattern of Failure

    Local failure is defined as relapse or progression of disease at the primary site. The cumulative incidence of local failure will be estimated; competing events will include distant failure or death prior to local failure.

    Measured: Up to 3 years

  3. Dose Limiting Toxicity (DLT) or Severe (Grade 3 or 4) VOD With hu14.18K322A With Allogeneic NK Cells in Consolidation

    Number of patients who experience an unacceptable dose limiting toxicity (per CTCAE v 4.0) including the following toxicities: 1) toxicity requiring the use of pressors, including Grade 4 acute capillary leak syndrome or Grade3 and 4 hypotension; 2) Toxicity requiring ventilation support, including Grade 4 respiratory toxicity; 3) Grade 3 or 4 neurotoxicity with MRI evidence of new CNS thrombi, infarction or bleeding in any subject receiving the hu14.18K322A with NK cell combination; 4) Failure of recovery of ANC > 500/mm3 by day 35 after PBSC infusion. Number of patients who experience Grade 3 or Grade 4 (per Common Toxicity Criteria v 4.0) veno occlusive disease (VOD).

    Measured: During the recovery phase after busulfan/melphalan and PBSC rescue (approximately 24-26 weeks after enrollment)

  4. Dose Limiting Toxicity (DLT)

    Number of patients who experience an unacceptable dose limiting toxicity (per CTCAE v 4.0) including the following toxicities: 1) Toxicity requiring the use of pressors, including Grade 4 acute capillary leak syndrome or Grade 3 and 4 hypotension; 2) Toxicity requiring ventilation support, including Grade 4 respiratory toxicity; 3) Grade 3 or 4 neurotoxicity with MRI evidence of new CNS thrombi, infarction or bleeding.

    Measured: During MRD treatment cycle (approximately 8-12 months after enrollment)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2013 (estimated)
  2. Study start5 Jul 2013
  3. Primary completion21 Oct 2021
  4. Study completion31 Dec 2025

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
153 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01857934
Sponsor's protocol ID
NB2012
Other IDs
NCI-2013-00034
Status last verified
Sep 2026
First submitted
16 May 2013
Last updated
22 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
Yes

Publications

  • Furman WL, McCarville B, Shulkin BL, Davidoff A, Krasin M, Hsu CW, Pan H, Wu J, Brennan R, Bishop MW, Helmig S, Stewart E, Navid F, Triplett B, Santana V, Santiago T, Hank JA, Gillies SD, Yu A, Sondel PM, Leung WH, Pappo A, Federico SM. Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A. J Clin Oncol. 2022 Feb 1;40(4):335-344. doi: 10.1200/JCO.21.01375. Epub 2021 Dec 6.

    PubMed 34871104

  • Nguyen R, Sahr N, Sykes A, McCarville MB, Federico SM, Sooter A, Cullins D, Rooney B, Janssen WE, Talleur AC, Triplett BM, Anthony G, Dyer MA, Pappo AS, Leung WH, Furman WL. Longitudinal NK cell kinetics and cytotoxicity in children with neuroblastoma enrolled in a clinical phase II trial. J Immunother Cancer. 2020 Mar;8(1):e000176. doi: 10.1136/jitc-2019-000176.

    PubMed 32221013

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in