Description:
An International, Open Label, Randomized, Controlled, Two-Arm, Multicenter Phase 3 Trial
Title
- Brief Title: IT With or Without Naxitamab and GM CSF in Patients With High-Risk Neuroblastoma
- Official Title: Irinotecan and Temozolomide With or Without Naxitamab and Granulocyte-Macrophage Colony Stimulating Factor in Patients With High-Risk Neuroblastoma With Primary Refractory Disease or in First Relapse. An International, Open Label, Randomized, Controlled, Two-Arm, Multicenter Phase 3 Trial
Clinical Trial IDs
- ORG STUDY ID:
203
- NCT ID:
NCT04560166
Conditions
Interventions
Drug | Synonyms | Arms |
---|
irinotecan and temozolomide and naxitamab and GM CSF | | irinotecan and temozolomide and naxitamab and GM CSF |
irinotecan and temozolomide | | irinotecan and temozolomide |
Purpose
An International, Open Label, Randomized, Controlled, Two-Arm, Multicenter Phase 3 Trial
Detailed Description
This is an open label, randomized, controlled, multicenter phase 3 trial, in patients ≥ 12
months of age with high-risk NB with primary refractory disease or in first relapse. Patients
will be randomized 2:1 to receive either IT + naxitamab + GM-CSF or IT alone. Patients
randomized to treatment with IT alone who either develop progressive disease or do not
achieve overall response at or during the initial 4 cycles or who discontinue IT treatment
due to toxicity, will be offered treatment with naxitamab + GM-CSF; naxitamab treatment can
be administered with IT (treatment group C) or without IT (Treatment group D), as applicable.
The Follow-Up period ends 2 years after randomization.
Trial Arms
Name | Type | Description | Interventions |
---|
irinotecan and temozolomide and naxitamab and GM CSF | Active Comparator | Each treatment cycle is 21 days | - irinotecan and temozolomide and naxitamab and GM CSF
|
irinotecan and temozolomide | Active Comparator | Each treatment cycle is 21 days | - irinotecan and temozolomide
|
Eligibility Criteria
Inclusion Criteria:
- 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
- One of the following:
- Measurable tumor on MRI, (CT) scan obtained within 3 weeks prior to randomization
that is MIBG-avid or demonstrates increased FDG uptake on PET scan
- MIBG (Metaiodobenzylguanidine) scan obtained within 3 weeks prior to
randomization 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
- Soft tissue disease that is not MIBG avid or does not demonstrate increased FDG
uptake on PET scan, but the presence of viable NB is documented by new biopsy
- Life expectancy of at least 6 months, as judged by the Investigator
- Written informed consent
Exclusion Criteria:
- Myelodysplastic syndrome or any malignancy other than NB
- Any systemic anti-cancer therapy within 3 weeks
- Autologous stem cell transplant (ASCT) or stem cell infusion within 6 weeks prior to
randomization or ongoing toxicity due to the ASCT/stem cell infusion at the discretion
of the investigator
- Therapeutic 131I-MIBG within 6 weeks prior to randomization
- Radiotherapy (RT) within 4 weeks prior to randomization 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
- 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 randomization
- 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)
- 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 randomization
- Life threatening infection(s)
- Uncontrolled seizure disorders despite anticonvulsant therapy (defined as a seizure
event within 3 months prior to randomization)
- Treatment with enzyme-inducing anticonvulsants including phenytoin, phenobarbital, or
carbamazepine for at least 7 days prior to randomization
- Concomitant use with St John's wort
- Allogeneic hematopoietic stem cell transplantation (allo-SCT) or
donor-lymphocyte-infusion (defined as any kind of active allogenic lymphocyte
suspension)
- Treatment with Hematopoietic Progenitor Cell (HPC) boost or "top-up" of allogenic stem
cells (lymphocyte-depleted) within 2 months prior to randomization
- History of allergy or known hypersensitivity to GM-CSF, yeast-derived products, or any
component of GM-CSF or naxitamab
- History of anaphylactic reactions CTCAE Grade 4 related to prior anti-GD2 antibody
therapy
- Unacceptable hematological status, unacceptable liver or kidney function prior to
first dosing
- Platelet count <75,000/µL
- 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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 12 Months |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Objective response rate (ORR) |
Time Frame: | 84 days |
Safety Issue: | |
Description: | The proportion of patients obtaining a centrally assessed complete response (CR) or partial response (PR) according to the International Neuroblastoma Response Criteria (INRC) |
Secondary Outcome Measures
Measure: | ORR after 2 cycles |
Time Frame: | 42 days |
Safety Issue: | |
Description: | The proportion of patients obtaining a centrally assessed CR or PR according to the INRC |
Measure: | Duration of response (DoR) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | The time from first centrally assessed OR (CR or PR according to the INRC) to PD or death |
Measure: | Complete response (CR) rate |
Time Frame: | 84 days |
Safety Issue: | |
Description: | the proportion of patients obtaining a centrally assessed CR according to the INRC |
Measure: | CR rate after 2 cycles |
Time Frame: | 42 days |
Safety Issue: | |
Description: | the proportion of patients obtaining a centrally assessed CR according to the INRC |
Measure: | Minor response (MR) rate |
Time Frame: | 84 days |
Safety Issue: | |
Description: | The proportion of patients obtaining a centrally assessed MR according to the INRC |
Measure: | MR or better rate |
Time Frame: | 84 days |
Safety Issue: | |
Description: | The proportion of patients obtaining a centrally assessed CR, PR, or MR according to the INRC |
Measure: | CR in Bone Marrow (BM) |
Time Frame: | 84 days |
Safety Issue: | |
Description: | Proportion of patients with BM disease at randomization who obtain CR in BM and convert to minimal residual disease (MRD) negative |
Measure: | Time to first subsequent anti-cancer treatment or death |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Time from initiation of IMP treatment to death or initiation of new anti-cancer treatment |
Measure: | Progression free survival (PFS) |
Time Frame: | 2 years |
Safety Issue: | |
Description: | The time from randomization until PD or death |
Measure: | PFS |
Time Frame: | 1 year |
Safety Issue: | |
Description: | The proportion of patients alive and with no PD |
Measure: | PFS at 2 years |
Time Frame: | 2 year |
Safety Issue: | |
Description: | The proportion of patients alive and with no PD |
Measure: | Overall survival (OS) |
Time Frame: | 1 year |
Safety Issue: | |
Description: | The proportion of patients alive |
Measure: | Overall survival (OS) at 2 years |
Time Frame: | 2 year |
Safety Issue: | |
Description: | The proportion of patients alive |
Measure: | Incidence of adverse events (AEs) and serious adverse events (SAEs) |
Time Frame: | 2 year |
Safety Issue: | |
Description: | Safety will be evaluated by the incidence of AEs and SAEs graded according to Common Terminology Criteria for AEs (CTCAE) version 5.0 |
Measure: | Incidence of anti-drug-antibodies (ADA) |
Time Frame: | 1 year |
Safety Issue: | |
Description: | ADA (including assessment for neutralizing potential) will be assessed |
Measure: | Number of naxitamab infusions done in an out-patient setting |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Number of naxitamab infusions not requiring admission to hospital due to AEs |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Not yet recruiting |
Lead Sponsor: | Y-mAbs Therapeutics |
Last Updated
October 2, 2020