Description:
131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for
neuroblastoma patients with refractory or relapsed disease. In this pediatric phase 1 trial,
131I-MIBG will be given in combination with dinutuximab, a chimeric 14.18 monoclonal
antibody. This study will utilize a traditional Phase I rolling 6 dose escalation design to
determine a recommended phase 2 pediatric dose. An expansion cohort of an additional 6
patients will then be enrolled. If tolerable, vorinostat will then be added to the third dose
level. A 6 patient expansion cohort may then be enrolled.
Title
- Brief Title: MIBG With Dinutuximab +/- Vorinostat
- Official Title: A Phase I Study of 131I-MIBG With Dinutuximab +/- Vorinostat for Relapsed/Refractory Neuroblastoma
Clinical Trial IDs
- ORG STUDY ID:
NANT2017-01
- NCT ID:
NCT03332667
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Ch14.18 Monoclonal Antibody | Chimeric Monoclonal Antibody 14.18, MAB Ch 14.18, Unituxin, Ch14.18, Dinutuximab | 131I-MIBG with Dinutuximab |
Vorinostat | Zolina | 131I-MIBG with Dinutuximab and Vorinostat |
Purpose
131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for
neuroblastoma patients with refractory or relapsed disease. In this pediatric phase 1 trial,
131I-MIBG will be given in combination with dinutuximab, a chimeric 14.18 monoclonal
antibody. This study will utilize a traditional Phase I rolling 6 dose escalation design to
determine a recommended phase 2 pediatric dose. An expansion cohort of an additional 6
patients will then be enrolled. If tolerable, vorinostat will then be added to the third dose
level. A 6 patient expansion cohort may then be enrolled.
Detailed Description
131I-Metaiodobenzylguanidine (131I-MIBG) is one of the most effective therapies utilized for
neuroblastoma patients with refractory or relapsed disease. Data from pre-clinical and adult
studies suggest that radiation can enhance the efficacy of immunotherapy and targeted
therapies such as dinutuximab. This first pediatric phase 1 trial of 131I-MIBG in combination
with dinutuximab and vorinostat aims to determine the recommended phase 2 pediatric dose of
these three therapies in combination.
Trial Arms
Name | Type | Description | Interventions |
---|
131I-MIBG with Dinutuximab | Experimental | Patients will receive 131I-MIBG on day 1. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab and 131I-MIBG dose will be based on the dose level assigned at the time of patient registration. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy | - Ch14.18 Monoclonal Antibody
|
131I-MIBG with Dinutuximab and Vorinostat | Experimental | Patients will receive vorinostat on days 0-13. 131I-MIBG will be received on day 1. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab and 131I-MIBG dose will be based on the dose level assigned at the time of patient registration. Patient will receive GM-CSF on days 8-17 and 29-38 at 250 mcg/m2. All patients will receive autologous hematopoietic stem cell infusion on day 15 (+/- 2) of therapy | - Ch14.18 Monoclonal Antibody
- Vorinostat
|
Eligibility Criteria
Inclusion Criteria:
- Patients must have a diagnosis of neuroblastoma either by histologic verification of
neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased
urinary catecholamines
- Patients must have high risk neuroblastoma according to COG risk classification at the
time of study registration. Patients who were initially considered low or intermediate
risk, but then reclassified as high risk are also eligible.
- Patients must have at least ONE of the following: 1) Recurrent/progressive disease at
any time prior to study enrollment, 2) Refractory disease, 3) Persistent disease
- Patients must have at least ONE of the following: 1) Bone disease, 2) Any amount of
neuroblastoma tumor cells in the bone marrow, 3) At least one soft tissue lesion that
meets criteria for a TARGET lesion, 4) At least one non-target soft tissue lesion that
is not measurable, but had a biopsy positive for neuroblastoma and/or
ganglioneuroblastoma at any time prior to enrollment or is MIBG avid
- Patients must have a Lansky (≤16 years) or Karnofsky (> 16 years) score of at least 50
- Patients must have fully recovered from the acute toxic effects of all prior
chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Patients must not have received any of the specified therapies as stated in the
protocol in the time period prior to registration
- Patients must not be receiving any other anti-cancer agents or radiotherapy at the
time of study entry or while on study.
- Patients must not be receiving other investigational medications (covered under
another IND) within 30 days of study entry or while on study.
- Patients must not be receiving chronic systemic corticosteroids at doses greater than
physiologic dosing (inhaled corticosteroids acceptable).
- Patient must meet the organ function and system function requirements as stated in the
protocol
Exclusion Criteria:
- Pregnancy, breast feeding, or unwillingness to use effective contraception during the
study.
- Patients who, in the opinion of the investigator, may not be able to comply with the
safety monitoring requirements of the study.
- Patients with disease of any major organ system that would compromise their ability to
withstand therapy.
- Patients who have received prior allogeneic stem cell transplant
- Patients who are on hemodialysis.
- Patients with an active or uncontrolled infection.
- Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or
hepatitis C.
- Patients and/or families who are physically and psychologically unable to cooperate
with the radiation safety isolation.
- Patients with a history of having to discontinue anti-GD2 antibody therapy due to
toxicity are not eligible.
- Prior anti-GD2 therapy is not otherwise an exclusionary criteria unless it was given
in combination with therapeutic 131I-MIBG.
- Patient declines participation in NANT 2004-05, the NANT Biology Study
Maximum Eligible Age: | 30 Years |
Minimum Eligible Age: | 1 Year |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Determination of maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of 131I-MIBG with Dinutuximab |
Time Frame: | Approximately 2 years |
Safety Issue: | |
Description: | By dose level.Two to six evaluable patients will be entered at each of the three dose levels for determination of the maximum tolerated dose. |
Secondary Outcome Measures
Measure: | Evaluation of overall response |
Time Frame: | Overall response is assessed at 8, 16, 24, 40, and 56 weeks from start of therapy, and then every 16 weeks, and at end of protocol therapy; an average of 24 weeks.] |
Safety Issue: | |
Description: | Overall response is the measure that will be used to assess anti-tumor activity, and is determined by integration of the soft tissue response, bone response, and bone marrow response according to the NANT Response Criteria, Version 2.0 definitions. Responders are defined as patients with an overall response of Complete Response, Complete Response-Minimal Disease, or Partial Response. |
Measure: | Evaluation of soft tissue response |
Time Frame: | Soft tissue response is assessed at 8, 16, 24, 40, and 56 weeks from start of therapy, and then every 16 weeks, and at end of protocol therapy; an average of 24 weeks |
Safety Issue: | |
Description: | Soft tissue response is assessed by CT/MRI scans using RECIST criteria to define measurable lesions with the addition of MIBG and/or FDG-PET (only for MIBG non-avid tumors) avidity and/or biopsy to define target lesions for response. |
Measure: | Evaluation of bone response |
Time Frame: | Bone response is assessed at 8, 16, 24, 40, and 56 weeks from start of therapy, and then every 16 weeks, and at end of protocol therapy; an average of 24 weeks |
Safety Issue: | |
Description: | Bone response is assessed by MIBG scans for MIBG avid tumors, and by FDG-PET scans for MIBG non-avid tumors, using sectors 1-9 of the Curie scoring to determine the relative score at each response timepoint. |
Measure: | Evaluation of bone marrow response |
Time Frame: | Bone marrow response is assessed at 8, 16, 24, 40, and 56 weeks from start of therapy, and then every 16 weeks, and at end of protocol therapy; an average of 24 weeks |
Safety Issue: | |
Description: | Bone marrow response is assessed by morphologic and immunohistologic evaluation of bilateral bone marrow aspirates and biopsies |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | New Approaches to Neuroblastoma Therapy Consortium |
Last Updated
January 20, 2021