Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT07261241 | NANT 2021-02: Randomized MIBG With Vorinostat/Dinutuximab/Vorinostat + Dinutuximab | PHASE2 | NOT YET_RECRUITING | 118 | — | — | Jul 31, 2026 | Jul 31, 2031 | Dec 3, 2025 | 13 | United States |
| NCT05421897 | Rapid Administration Pilot for Infusing Dinutuximab | PHASE1 | ACTIVE NOT_RECRUITING | 11 | — | — | Nov 29, 2022 | Jan 1, 2026 | Jan 29, 2026 | 1 | United States |
| NCT02573896 | Immunotherapy of Relapsed Refractory Neuroblastoma With Expanded NK Cells | PHASE1 | ACTIVE NOT_RECRUITING | 13 | — | — | Jan 14, 2019 | Dec 1, 2026 | Mar 23, 2026 | 11 | United States |
| NCT03332667 | MIBG With Dinutuximab +/- Vorinostat | PHASE1 | COMPLETED | 45 | — | — | Sep 12, 2018 | Feb 23, 2024 | Apr 16, 2025 | 12 | United States |
To identify the MIBG treatment regimen associated with the highest overall response rate after one course of treatment on the three arms. The response evaluation was based on central review (intent to treat analysis). Responders defined as meeting CR/MRD/PR criteria. Response was based on NANT response criteria v1.2 (https://doi.org/10.1002/pbc.26940). RECST 1.1 criteria was used for measurable tumors with PR criteria \> 30% decrease in target tumor size. Curie score was used with PR criteria \> 50% decrease in Curie score. Complete Response- disappearance of all target lesions, Curie score of 0 and no detectable bone marrow disease. Overall Response (OR)=CR+PR.
The number of dinutuximab days tolerated in 4 hours or less in Cycle 1 will be measured
The infusion time of dinutuximab days administered on Days 1-4 will be measured and the average infusion time will be calculated for each dinutuximab day during Cycle 1.
Proportion of patients whose NK cell product is at least 80% of 10\^7 NK cells per kg (sufficient cells to give at least 1 dose at the lowest dose level).
Proportion of patients whose NK cell product is at least 80% of the planned dose for one dose
Proportion of patients with any Grade 3 or greater non-hematological toxicities on any course
Proportion of patients with Course 1 DLT in Cohort A
Proportion of patients with Course 1 DLT in Cohort B
Proportion of patients with any grade 3 or greater non-hematological toxicities in Cohort A
Proportion of patients with any grade 3 or greater non-hematological toxicities in Cohort B
| Arm | Type | Description |
|---|---|---|
| Arm A: 131I-MIBG + vorinostat | EXPERIMENTAL | Patients assigned to Arm A will receive vorinostat orally once daily on Days 0 to 13 at a dose of 180 mg/m2/dose (maximum dose 400 mg). Patients will receive 131I-MIBG 18 mCi/kg (maximum dose 1200 mCi) on Day 1 and autologous stem cell infusion on Day 15 (plus 2 days or minus 1 day, hereafter abbreviated as +2/-1 days). There must be at least 24 hours between the last dose of vorinostat and stem cell infusion. Disease evaluation is to occur between days 50-60. The time interval between performing end of Course 1 disease evaluation and administration of Course 2 131I-MIBG is not to exceed 4 weeks. |
| Arm B: 131I-MIBG + dinutuximab | EXPERIMENTAL | Patients assigned to Arm B will receive 18 mCi/kg (maximum dose 1200 mCi) 131I-MIBG on Day 1 and autologous stem cell infusion on Day 15 (+2/-1 days). Dinutuximab 17.5 mg/m2/day is given intravenously on Days 8-11 and 29-32 of therapy. Disease evaluation is to occur between Days 50-60. In case of treatment delays with dinutuximab during Course 1, the time interval between performing end of Course 1 disease evaluation and administration of Course 2 131I-MIBG is not to exceed 4 weeks. |
| Arm C: 131I-MIBG + vorinostat + dinutuximab | EXPERIMENTAL | Patients assigned to Arm C will receive vorinostat 180 mg/m2/dose (maximum dose 400 mg) on Days 0 to 13, 131I-MIBG 18 mCi/kg (maximum dose 1200 mCi) on Day 1. Dinutuximab 17.5 mg/m2/day is given intravenously on Days 8-11 and 29-32 of therapy. Disease evaluation is to occur between Days 50-60. In case of treatment delays with dinutuximab during Course 1, the time interval between performing end of Course 1 disease evaluation and administration of Course 2 131I-MIBG is not to exceed 4 weeks. |
| Rapid infusion of dinutuximab with chemotherapy | EXPERIMENTAL | Patients will receive chemotherapy and dinutuximab via rapid infusion |
| NK cells with Dinutuximab & Lenalidomide | EXPERIMENTAL | Patients in this arm will receive a designated dose of NK cells on Day 5 and 17.5 mg/m2/dose of dinutuximab on Day 1-4. Patients on Dose Level 4 will also receive 25mg/m2/dose of Lenalidomide during Day -6 through 14 of treatment. |
| Cohort A DL1 | EXPERIMENTAL | Patients will receive 131I-MIBG on day 1 at 12 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. 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 |
| Cohort A DL2 | EXPERIMENTAL | Patients will receive 131I-MIBG on day 1 at 15 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. 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 |
| Cohort A DL3 | EXPERIMENTAL | Patients will receive 131I-MIBG on day 1 at 18 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. 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 |
| Cohort B DL4 | EXPERIMENTAL | Vorinostat will be given on days 0-13 at 180 mg/m2/dose. Patients will receive 131I-MIBG on day 1 at 18 mCi/kg/dose. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy at 17.5 mg/m2/dose. 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 |
| Name | Type | Description |
|---|---|---|
| Radiation: 131I-MIBG | DRUG | Patients will receive 131I-MIBG 18 mCi/kg (maximum dose 1200 mCi) on Day 1 |
| Dinutuximab | DRUG | Dinutuximab 17.5 mg/m2/day is given intravenously on Days 8-11 and 29-32 of therapy |
| Vorinostat | DRUG | Vorinostat will be given on days 0-13 at a dose of 180 mg/m2/dose (maximum dose 400 mg). |
| Dinutuximab with Chemotherapy | DRUG | Rapid infusion of dinutuximab in 5 hours or less |
| NK Cells | BIOLOGICAL | The designated dose of NK Cells will be infused on Day 5 by IV drip using a Y infusion set with a filter-less chamber. Cells should not be delivered at a rate faster than 10 ml/kg/hr (as determined by drip rate or syringe push rate), and should not take longer than one hour for total infusion time if possible. |
| Lenalidomide | DRUG | 25 mg/m2/day of Lenalidomide will be given at Dose Level 4, once daily with or without food by mouth on days -6 through +14. |
| 131I-MIBG | RADIATION | Patients will receive 131I-MIBG on day 1. 131I-MIBG dose will be based on the dose level assigned at the time of patient registration |
| Sargramostim | DRUG | Sargramostim (GM-CSF) will be given on day 8-17 at 250 mcg/m\^2 |
| Potassium Iodide | DRUG | Potassium iodide will be given by mouth at a dose of 6mg/kg 8-12 hours prior to infusion of 131I-MIBG on Day 1 and then 1mg/kg/dose by mouth starting 4-6 hours after completion of MIBG infusion and continuing every 4 hours on protocol days 1-7 and then 1mg/kg/dose by mouth once daily on protocol days 8-45 |
Inclusion Criteria: Age Patients must be ≥ 1 year and \< 30 years of age at the time of study registration. Diagnosis Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma nodular subtype either by histologic verification of neuroblastoma and/or demonstration of tumor cells in th...