Clinical Trials /

IT With or Without Naxitamab and GM CSF in Patients With High-Risk Neuroblastoma

NCT04560166

Description:

An International, Open Label, Randomized, Controlled, Two-Arm, Multicenter Phase 3 Trial

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

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

  • Neuroblastoma Recurrent

Interventions

DrugSynonymsArms
irinotecan and temozolomide and naxitamab and GM CSFirinotecan and temozolomide and naxitamab and GM CSF
irinotecan and temozolomideirinotecan 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

NameTypeDescriptionInterventions
irinotecan and temozolomide and naxitamab and GM CSFActive ComparatorEach treatment cycle is 21 days
  • irinotecan and temozolomide and naxitamab and GM CSF
irinotecan and temozolomideActive ComparatorEach 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