Study of Chemoimmunotherapy for High-Risk Neuroblastoma

Sponsor

Memorial Sloan Kettering Cancer Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03189706

Collaborator

Y-Mabs, Inc (Other)

Enrollment

Location

Arm

71.6

Anticipated Duration (Months)

0.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to find out whether an experimental drug called Hu3F8 can be given with the chemotherapy drugs irinotecan and temozolomide and another drug called GM-CSF. The investigators want to find out if this combination is safe and what effect it has on the participant and the disease.

Condition or Disease	Intervention/Treatment	Phase
Neuroblastoma (NB)	Drug: Irinotecan Drug: temozolomide Biological: Hu3F8 Drug: GM-CSF	Early Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

48 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

This is a pilot study of HITS in patients with resistant NB.This is a pilot study of HITS in patients with resistant NB.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase II Study of Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS) Chemoimmunotherapy for High-Risk Neuroblastoma

Actual Study Start Date :

Jun 12, 2017

Anticipated Primary Completion Date :

Jun 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS) Each cycle consists of four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF.	Drug: Irinotecan 50mg/m^2/day IV will be administered from day 1-5 Drug: temozolomide (given concurrently with Irinotecan) 150mg/m^2/day orally Biological: Hu3F8 2.25mg/kg IV will be administered on days 2, 4, 8 and 10 Drug: GM-CSF 250mcg/m2/day SC will be administered on days 6-10

Arm

Intervention/Treatment

Experimental: Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS)

Each cycle consists of four doses of hu3F8, five doses each of irinotecan and temozolomide and five doses of GM-CSF.

Drug: Irinotecan

50mg/m^2/day IV will be administered from day 1-5

Drug: temozolomide

(given concurrently with Irinotecan) 150mg/m^2/day orally

Biological: Hu3F8

2.25mg/kg IV will be administered on days 2, 4, 8 and 10

Drug: GM-CSF

250mcg/m2/day SC will be administered on days 6-10

Outcome Measures

Primary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [2 years]
The regimen will be considered safe if there are no toxicities requiring discontinuation of therapy in at least 9/10 patients during the first two cycles.
response rate (CR+PR) [2 years]
Response assessment will be based on the best response over the course of four cycles. Disease response for NB will use the International NB Response Criteria. Patients who withdraw from the study prior to cycle 4 with < partial response will also not be considered evaluable for response and will be replaced.

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 international criteria,.e., histopathology (confirmed by the MSK Department of Pathology) or bone marrow metastases plus high urine catecholamine levels
High-risk NB as defined as any of the following:
Stage 4 with MYCN amplification (any age)
Stage 4 without MYCN amplification (>1.5 years of age)
Stage 3 with MYCN amplification (unresectable; any age)
Stage 4S with MYCN amplification (any age)
Patients fulfill one of the following criteria:

Have evidence of soft tissue disease OR
If they only have osteomedullary disease at protocol enrollment, they should have:

Had previously received Hu3F8+GMCSF therapy AND have had less than a complete response to it OR
Had progressed progressive disease after their most recent anti-neuroblastoma therapeutic regimen
Patients must have evaluable (microscopic marrow metastasis, elevated tumor markers, positive MIBG or PET scans) or measurable (CT, MRI) disease documented after completion of prior systemic therapy.
Prior treatment with murine and hu3F8 is allowed.
Prior treatment with irinotecan or temozolomide is permitted.
Patients with prior m3F8, hu3F8, ch14.18 or hu14.18 treatment must have a negative HAHA antibody titer. Human anti-mouse antibody positivity is allowed.
Signed informed consent indicating awareness of the investigational nature of this program.

Exclusion Criteria:

Patients with CR/VGPR disease
Existing severe major organ dysfunction, i.e., renal, cardiac, hepatic, neurologic, pulmonary, or gastrointestinal toxicity ≥ grade 3 except for hearing loss, alopecia, anorexia, nausea, and hypomagnesemia from TPN, which may be grade 3
ANC < 500/uL
Platelet count <30K/uL
History of allergy to mouse proteins
Active life-threatening infection
Inability to comply with protocol requirements
Women who are pregnant or breast-feeding