Clinical Trials /

Naxitamab and GM-CSF in Combination With IT in Patients With High-Risk Neuroblastoma

NCT04560166

Description:

An International, Single-Arm, Multicenter Phase 2 Trial.

Related Conditions:
  • Neuroblastoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Naxitamab and GM-CSF in Combination With IT in Patients With High-Risk Neuroblastoma
  • 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.

Clinical Trial IDs

  • ORG STUDY ID: 203
  • NCT ID: NCT04560166

Conditions

  • Neuroblastoma Recurrent

Interventions

DrugSynonymsArms
Naxitamab and GM-CSF in combination with irinotecan and temozolomideNaxitamab and GM-CSF in combination with irinotecan and temozolomide

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Naxitamab and GM-CSF in combination with irinotecan and temozolomideExperimentalA 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.
  • Naxitamab and GM-CSF in combination with 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, 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

               -  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

        Exclusion Criteria:

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:12 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall 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 overall response (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:Time to first subsequent therapy
Time Frame:3 years
Safety Issue:
Description:the time from initiation of IMP treatment until death or start of new anti-cancer treatment (prohibited as per protocol)
Measure:Progression free survival (PFS)
Time Frame:3 years
Safety Issue:
Description:the time from enrollment until progressive disease or death, whichever comes first
Measure:PFS at 1 year
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:3 years
Safety Issue:
Description:the time from enrollment until death
Measure:Overall survival (OS)
Time Frame:1 year
Safety Issue:
Description:the time from enrollment until death
Measure:Overall survival (OS) at 2 years
Time Frame:2 year
Safety Issue:
Description:The proportion of patients alive

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Y-mAbs Therapeutics

Last Updated

July 14, 2021