Neuroblastoma RecurrentPhase 2NCT04560166
Naxitamab and GM-CSF in Combination With IT in Patients With High-Risk Neuroblastoma
A Phase 2 study testing Naxitamab and GM-CSF in combination with irinotecan and temozolomide in people with Neuroblastoma Recurrent, run by Y-mAbs Therapeutics at 3 sites in 2 countries.
Trial summary
An International, Single-Arm, Multicenter Phase 2 Trial. Read more about this study
- Who is it for?
- Ages 12 months and older
- Conditions the study is for
- Neuroblastoma Recurrent
- What is being tested?
- Naxitamab and GM-CSF in combination with irinotecan and temozolomide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 3 sitesin 2 countries
- Study dates
- 8 Nov 2021to 21 Sep 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 12 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Neuroblastoma (NB)
- Documented high-risk disease
- Receipt of Standard of Care (SoC) frontline induction/consolidation therapy (including surgery, chemotherapy, ASCT, MIBG, radiotherapy, immunotherapy, or retinoids)
- Active disease despite previous aggressive multi-drug chemotherapy, defined as one of the following:
- verified first progression during multi-drug frontline treatment or
- verified first episode of relapse, defined as recurrence after response to frontline treatment, or
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- verified first designation of refractory disease, defined as persistent metastatic disease (SD or minor response by INRC and MIBG curie score ≥3) detected at conclusion of at least 4 cycles of multi-drug induction chemotherapy on or according to a high-risk NB treatment protocol as defined above
- The patients must have one of the following (locally assessed) obtained within 3 weeks prior to enrollment and at least 10 calendar days after end of any prior anti-cancer treatment:
- Measurable tumor on CT/MRI scan that is MIBG-avid or demonstrates increased FDG uptake on PET scan
- MIBG (Metaiodobenzylguanidine) scan with positive uptake at a minimum of one site. This site must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction
- Age ≥ 12 months at enrollment
- Written informed consent
Who cannot join
- Myelodysplastic syndrome or any malignancy other than NB
- Any systemic anti-cancer therapy within 3 weeks
- Autologous stem cell transplant (ASCT) within 6 weeks prior to enrollment or ongoing toxicity due to the stem cell transplant at the discretion of the investigator
- Therapeutic 131I-MIBG within 6 weeks prior to enrollment
- Radiotherapy (RT) within 4 weeks prior to enrollment at any lesion site that will be identified as a target lesion to measure tumor response
- Prior treatment with anti-GD2 if the patient experienced Progressive Disease (PD) while on anti-GD2 treatment
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- Receipt of second line chemotherapy after designation of primary refractory disease or first relapse or PD
- NB in Bone Marrow (BM) only
- NB in the Central Nervous System (CNS) or leptomeningeal disease within 6 months prior to enrollment
- Performance status of < 50% as per the Lansky scale (patients less than 16 years of age) or Karnofsky scale (for patients aged 16 years or older)
- Life expectancy of less than 6 months
- Left ventricular ejection fraction < 50% by echocardiography
- Inadequate pulmonary function
- Diarrhea Grade ≥ 2
- Treatment with long-acting myeloid growth factor within 14 days or short-acting myeloid growth factor within 7 days prior to first dose of GM-CSF
- Receipt of immunosuppressive treatment (local steroids excluded) within 4 weeks prior to enrollment
- Life threatening infection(s)
- Uncontrolled seizure disorders despite anticonvulsant therapy (defined as a seizure event within 3 months prior to enrollment)
- Treatment with enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to enrollment
- Concomitant use with St John's wort
- Allogeneic hematopoietic stem cell transplantation (allo-SCT) or donor-lymphocyte-infusion (defined as any kind of active allogeneic lymphocyte suspension)
- Treatment with Hematopoietic Progenitor Cell (HPC) boost within 2 months prior to enrollment
- History of allergy or known hypersensitivity to GM-CSF, yeast-derived products, or any component of GM-CSF, naxitamab, irinotecan or temozolomide
- History of anaphylactic reactions CTCAE Grade 4 related to prior anti-GD2 antibody therapy
- Unacceptable hematological status at screening, defined as one of the following:
- Hemoglobin <5.0 mmol/L (<8 g/dL)
- White blood cell count <1000/µL
- Absolute neutrophil count <750/µL
- Platelet count < 75,000/µL
- Unacceptable liver function at screening, defined as one of the following:
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >5 times upper normal limit (UNL)
- Total bilirubin >1.5 x UNL
- Unacceptable kidney function at screening, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 calculated by the 2009 revised Bedside Schwartz Equation
- Inability to comply with protocol
- Significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of trial agents or to significantly increase the severity of the toxicities experienced from trial treatment
- Females of childbearing potential who are pregnant, breast feeding, intend to become pregnant, or are not using adequate contraceptive methods or males who are not using adequate contraceptive methods
Trial locations and contacts
3 sites in 2 countries.
3 sites in 2 countries
South Korea2 sites
Asan Medical Center Children's Hospital
Seoul
Seoul National University Hospital
Seoul
About this study
Official title: Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor in Combination With Irinotecan and Temozolomide in Patients With High-Risk Neuroblastoma With Primary Refractory Disease or in First Relapse. An International, Single-Arm, Multicenter Phase 2 Trial.
An International, Single-Arm, Multicenter Phase 2 Trial.
Read the detailed description
This is an international, single-arm, multicenter phase 2 trial, in patients ≥ 12 months of age with high-risk NB with primary refractory disease or in first relapse. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. The Follow-Up period ends 2 years after End of Treatment.
- Conditions
- Neuroblastoma Recurrent
- Being tested
- Naxitamab and GM-CSF in combination with irinotecan and temozolomide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Naxitamab and GM-CSF in combination with irinotecan and temozolomideDrug
- Irinotecan, solution for infusion (20 mg/mL)
- Temozolomide, capsules (5 mg, 20 mg and 100 mg)
- The humanized immunoglobulin isotype G (IgG1) monoclonal antibody (mAb) naxitamab, solution for infusion (4 mg/mL)
- Sargramostim (GM-CSF), lyophilized 250 µg single use vial (250 µg/vial)
| Study group | Role | What they receive |
|---|---|---|
| Naxitamab and GM-CSF in combination with irinotecan and temozolomide | Experimental | A treatment cycle is 21 days. The patients will receive irinotecan 50 mg/m2/day IV and temozolomide 100 mg/m2/day orally (both on Days 1-5) in combination with naxitamab 2.25 mg/kg/day IV (Days 2, 4, 8 and 10) (total 9 mg/kg per cycle), and GM-CSF 250 ug/m2/day sc, (Days 6-10).
Patients will receive up to 18 IT cycles after enrollment. Naxitamab and GM-CSF will be given for at least 8 cycles. Receives: Drug: Naxitamab and GM-CSF in combination with irinotecan and temozolomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Response Rate (ORR)
The proportion of patients obtaining a centrally assessed complete response (CR) or partial response (PR) according to the International Neuroblastoma Response Criteria (INRC)
Measured: 84 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Sep 2020
- Study start8 Nov 2021
- Primary completion21 Sep 2022
- Study completion21 Sep 2022
Why it stopped: Due to business priorities
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Neuroblastoma RecurrentStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Y-mAbs Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04560166
- Sponsor's protocol ID
- 203
- Status last verified
- Feb 2024
- First submitted
- 17 Sep 2020
- Last updated
- 18 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor in Combination With Irinotecan and Temozolomide in Patients With High-Risk Neuroblastoma With Primary Refractory Disease or in First Relapse. An International, Single-Arm, Multicenter Phase 2 Trial.
- ClinicalTrials.gov ID
- NCT04560166
- Acronym / sponsor ID
- 203
- Conditions
- Neuroblastoma Recurrent
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Due to business priorities
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Y-mAbs TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 8 Nov 2021 (actual)
- Primary completion
- 21 Sep 2022 (actual)
- Study completion
- 21 Sep 2022 (actual)
- First posted
- 23 Sep 2020 (actual)
- Results
- Posted 18 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An International, Single-Arm, Multicenter Phase 2 Trial.
Detailed description
This is an international, single-arm, multicenter phase 2 trial, in patients ≥ 12 months of age with high-risk NB with primary refractory disease or in first relapse. Patients will receive naxitamab + GM-CSF + irinotecan/temozolomide. The Follow-Up period ends 2 years after End of Treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Naxitamab and GM-CSF in combination with irinotecan and temozolomide | Experimental | Drug: Naxitamab and GM-CSF in combination with irinotecan and temozolomideA treatment cycle is 21 days. The patients will receive irinotecan 50 mg/m2/day IV and temozolomide 100 mg/m2/day orally (both on Days 1-5) in combination with naxitamab 2.25 mg/kg/day IV (Days 2, 4, 8 and 10) (total 9 mg/kg per cycle), and GM-CSF 250 ug/m2/day sc, (Days 6-10). Patients will receive up to 18 IT cycles after enrollment. Naxitamab and GM-CSF will be given for at least 8 cycles. |
Who may qualify
- Ages
- 12 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (12 listed)
- Neuroblastoma (NB)
- Documented high-risk disease
- Receipt of Standard of Care (SoC) frontline induction/consolidation therapy (including surgery, chemotherapy, ASCT, MIBG, radiotherapy, immunotherapy, or retinoids)
- Active disease despite previous aggressive multi-drug chemotherapy, defined as one of the following:
- The patients must have one of the following (locally assessed) obtained within 3 weeks prior to enrollment and at least 10 calendar days after end of any prior anti-cancer treatment:
Key exclusion criteria (36 listed)
- Myelodysplastic syndrome or any malignancy other than NB
- Any systemic anti-cancer therapy within 3 weeks
- Autologous stem cell transplant (ASCT) within 6 weeks prior to enrollment or ongoing toxicity due to the stem cell transplant at the discretion of the investigator
- Therapeutic 131I-MIBG within 6 weeks prior to enrollment
- Radiotherapy (RT) within 4 weeks prior to enrollment at any lesion site that will be identified as a target lesion to measure tumor response
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 |
|---|---|---|
| Naxitamab and GM-CSF in combination with irinotecan and temozolomide* Irinotecan, solution for infusion (20 mg/mL) * Temozolomide, capsules (5 mg, 20 mg and 100 mg) * The humanized immunoglobulin isotype G (IgG1) monoclonal antibody (mAb) naxitamab, solution for infusion (4 mg/mL) * Sargramostim (GM-CSF), lyophilized 250 µg single use vial (250 µg/vial) | Drug | Naxitamab and GM-CSF in combination with irinotecan and temozolomide |
Primary outcome
Overall Response Rate (ORR)
Time frame: 84 days
The proportion of patients obtaining a centrally assessed complete response (CR) or partial response (PR) according to the International Neuroblastoma Response Criteria (INRC)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
The record lists no contact. Use the official record to reach the sponsor.
3 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Naxitamab and GM-CSF in combination with irinotecan and temozolomide in people with Neuroblastoma Recurrent, run by Y-mAbs Therapeutics at 3 sites in 2 countries.
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 12 inclusion and 36 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 18 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in South Korea, Hong Kong. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Overall Response Rate (ORR) (time frame: 84 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 18 Mar 2024.