A Study of the Effect of Hu3F8/GM-CSF Immunotherapy Plus Isotretinoin in Patients in First Remission of High-Risk Neuroblastoma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03033303

Collaborator

Y-mAbs Therapeutics (Industry)

Enrollment

Location

Arm

76.2

Anticipated Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to test see the combined effects of the study drug called Humanized 3F8 (Hu3F8) when used with granulocyte-macrophage colony stimulating factor (GM-CSF). Hu3F8 plus GM-CSF could prevent your neuroblastoma from growing, but it could also cause side effects.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma	Biological: Hu3F8 Drug: GM-CSF Drug: Isotretinoin	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

59 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

In this phase II single arm trial, patients with HR-NB in first CR or VGPR undergo consolidation by using hu3F8/GM-CSF.In this phase II single arm trial, patients with HR-NB in first CR or VGPR undergo consolidation by using hu3F8/GM-CSF.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Hu3F8/GM-CSF Immunotherapy Plus Isotretinoin for Consolidation of First Remission of Patients With High-Risk Neuroblastoma: A Phase II Study

Actual Study Start Date :

Jan 23, 2017

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hu3F8/GM-CSF Plus Isotretinoin In this phase II single arm trial, patients with HR-NB in first CR or VGPR undergo consolidation by using hu3F8/GM-CSF x5 cycles and isotretinoin x6 cycles. Isotretinoin starts after cycle 2 of hu3F8/GM-CSF.	Biological: Hu3F8 Day 1: hu3F8 infused iv over ~30 to 90 minutes. Day 3: hu3F8 infused iv over ~30 to 90 minutes. Day 5: hu3F8 infused iv over ~30 to 90 minutes. Drug: GM-CSF Days -4 to 0: GM-CSF 250 mcg/m2/day, subcutaneously. Days 1 to 5: GM-CSF 500 mcg/m2/day, subcutaneously. Drug: Isotretinoin Isotretinoin is administered at 160 mg/m2/d, divided into two doses, x14 days.

Arm

Intervention/Treatment

Experimental: Hu3F8/GM-CSF Plus Isotretinoin

In this phase II single arm trial, patients with HR-NB in first CR or VGPR undergo consolidation by using hu3F8/GM-CSF x5 cycles and isotretinoin x6 cycles. Isotretinoin starts after cycle 2 of hu3F8/GM-CSF.

Biological: Hu3F8

Day 1: hu3F8 infused iv over ~30 to 90 minutes. Day 3: hu3F8 infused iv over ~30 to 90 minutes. Day 5: hu3F8 infused iv over ~30 to 90 minutes.

Drug: GM-CSF

Days -4 to 0: GM-CSF 250 mcg/m2/day, subcutaneously. Days 1 to 5: GM-CSF 500 mcg/m2/day, subcutaneously.

Drug: Isotretinoin

Isotretinoin is administered at 160 mg/m2/d, divided into two doses, x14 days.

Outcome Measures

Primary Outcome Measures

relapse-free survival (RFS) [2 years]
Patients are considered a response failure under this protocol if progressive disease is evident before two years. Deaths from toxicity attributable to protocol treatment will be counted as events. Patients who withdraw or are lost to followup before two years will be considered as progressions.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Diagnosis of NB as defined by a) histopathology (confirmed by the MSK Department of Pathology), or b) BM metastases or MIBG-avid lesion(s) plus high urine catecholamine levels.
Patients must have high-risk NB (MYCN-amplified stage 2/3/4/4S of any age and MYCN-nonamplified stage 4 in patients greater than 18 months of age).
Patients must be in first CR/VGPR
Patients must have a negative human anti-hu3F8 antibody (HAHA) titer

Exclusion Criteria:

Existing major organ dysfunction, i.e., renal., cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade 3, with the exception of hearing loss and hematologic toxicity.
Active life-threatening infection.
Inability to comply with protocol requirements