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

NCT ID: NCT04560166

Last Updated: 2024-03-18

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 2 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-08
• Study Completion Date: 2022-09-21

Brief Summary

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.

Conditions

Neuroblastoma Recurrent

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Naxitamab and GM-CSF in combination with irinotecan and temozolomide

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.

Group Type: EXPERIMENTAL

Naxitamab and GM-CSF in combination with irinotecan and temozolomide

Intervention Type: DRUG

• 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)

Interventions

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)

Intervention Type: DRUG

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
• 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

• Minimum Eligible Age: 12 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Y-mAbs Therapeutics

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Hong Kong Children's Hospital

Hong Kong, , Hong Kong

Asan Medical Center Children's Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Countries

Hong Kong; South Korea

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

203

Identifier Type: -

Identifier Source: org_study_id