Clinical trial NCT03189706: Study of Chemoimmunotherapy for High-Risk Neuroblastoma
Official title: Phase II Study of Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS) Chemoimmunotherapy for High-Risk Neuroblastoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: EARLY_PHASE1
Conditions: Neuroblastoma (NB)
Keywords: Hu3F8
Irinotecan
Temozolomide
Sargramostim
Chemoimmunotherapy
17-251
Lead sponsor: Memorial Sloan Kettering Cancer Center
Sponsor class: OTHER
Collaborators: name: Y-mAbs Therapeutics
First posted: 2017-06-16
Enrollment: 48
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a pilot study of HITS in patients with resistant NB.
Primary purpose: TREATMENT

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.


Eligibility criteria: 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:

  1. Have evidence of soft tissue disease OR
  2. 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

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
timeFrame: 2 years
measure: response rate (CR+PR)
timeFrame: 2 years
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
Study officials:
affiliation: Memorial Sloan Kettering Cancer Center
name: Shakeel Modak, MD
role: PRINCIPAL_INVESTIGATOR
References: