Back to results

Study of Chemoimmunotherapy for High-Risk Neuroblastoma

Primary Purpose

Neuroblastoma (NB)

Status

Active

Phase

Early Phase 1

Locations

United States

Study Type

Interventional

Intervention

Irinotecan

temozolomide

Hu3F8

GM-CSF

About this trial

This is an interventional treatment trial for Neuroblastoma (NB) focused on measuring Hu3F8, Irinotecan, Temozolomide, Sargramostim, Chemoimmunotherapy, 17-251

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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:
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

Sites / Locations

Memorial Sloan Kettering Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS)

Arm Description

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

Outcomes

Primary Outcome Measures

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

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)

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.

Secondary Outcome Measures

Full Information

NCT ID

NCT03189706

First Posted

June 13, 2017

Last Updated

September 11, 2023

Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Y-mAbs Therapeutics

1. Study Identification

Unique Protocol Identification Number

NCT03189706

Brief Title

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

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

June 12, 2017 (Actual)

Primary Completion Date

June 2024 (Anticipated)

Study Completion Date

June 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Memorial Sloan Kettering Cancer Center

Collaborators

Y-mAbs Therapeutics

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Neuroblastoma (NB)

Keywords

Hu3F8, Irinotecan, Temozolomide, Sargramostim, Chemoimmunotherapy, 17-251

7. Study Design

Primary Purpose

Treatment

Study Phase

Early Phase 1

Interventional Study Model

Single Group Assignment

Model Description

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

Masking

None (Open Label)

Allocation

N/A

Enrollment

48 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Hu3F8, Irinotecan/Temozolomide and Sargramostim (HITS)

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Irinotecan

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

temozolomide

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

Hu3F8

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

GM-CSF

Intervention Description

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

Primary Outcome Measure Information:

Title

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

Description

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.

Time Frame

2 years

Title

response rate (CR+PR)

Description

Time Frame

2 years

10. Eligibility

Sex

All

Accepts Healthy Volunteers

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: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Shakeel Modak, MD

Organizational Affiliation

Memorial Sloan Kettering Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Memorial Sloan Kettering Cancer Center

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Links:

URL

http://www.mskcc.org/mskcc/html/44.cfm

Description

Memorial Sloan Kettering Cancer Center

Learn more about this trial

Study of Chemoimmunotherapy for High-Risk Neuroblastoma

We'll reach out to this number within 24 hrs