Trials / Not Yet Recruiting
Not Yet RecruitingNCT07437963
Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse
Phase 1/2 Study of Dinutuximab/Cyclophosphamide/Topotecan/Sargramostim (GM-CSF) With or Without Iberdomide in Children With Relapsed, Refractory, or Progressive Neuroblastoma Following Prior Chemoimmunotherapy
- Status
- Not Yet Recruiting
- Phase
- Phase 1 / Phase 2
- Study type
- Interventional
- Enrollment
- 76 (estimated)
- Sponsor
- National Cancer Institute (NCI) · NIH
- Sex
- All
- Age
- 1 Year – 30 Years
- Healthy volunteers
- Not accepted
Summary
This phase I/II trial studies the side effects and best dose of iberdomide when given together with chemoimmunotherapy drugs and to see how well it works in treating patients with neuroblastoma that has come back after a period of improvement (relapsed), that does not respond to treatment (refractory), or that is growing, spreading, or getting worse (progressive) following prior chemoimmunotherapy. Iberdomide is a cereblon-modulating agent. It works by helping the immune system kill tumor cells. Chemoimmunotherapy is chemotherapy combined with immunotherapy. Chemotherapy drugs, such as cyclophosphamide and topotecan, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with dinutuximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Granulocyte-macrophage colony-stimulating factors (GM-CSF), such as sargramostim, may increase the production of blood cells and may help the immune system recover from the side effects of chemotherapy. Giving iberdomide with chemoimmunotherapy may be safe, tolerable, and/or effective in treating patients with relapsed, refractory, or progressive neuroblastoma following prior chemoimmunotherapy.
Detailed description
PRIMARY OBJECTIVES: I. To identify a recommended phase 2 dose (RP2D) of iberdomide administered in combination with dinutuximab, cyclophosphamide, topotecan, and GM-CSF in patients with relapsed, refractory, or progressive neuroblastoma previously treated with chemoimmunotherapy. (Phase 1 dose escalation) II. To evaluate whether the addition of iberdomide to dinutuximab, cyclophosphamide, topotecan, and GM-CSF is associated with an improved response rate compared to dinutuximab, cyclophosphamide, topotecan, and GM CSF in patients with refractory, relapsed, or progressive neuroblastoma previously treated with chemoimmunotherapy. (Phase 2 efficacy) SECONDARY OBJECTIVES: I. To evaluate the preliminary response rate of the addition of iberdomide to dinutuximab, cyclophosphamide, topotecan, and GM-CSF in patients with refractory, relapsed, or progressive neuroblastoma previously treated with chemoimmunotherapy. (Phase 1 dose escalation) II. To compare progression-free survival (PFS), overall survival (OS), confirmed response rate, and duration of response (DOR) between patients receiving dinutuximab, cyclophosphamide, topotecan, and GM-CSF with and without the addition of iberdomide. III. To describe the toxicity profile of the combination of dinutuximab, cyclophosphamide, topotecan, and GM-CSF with and without iberdomide. EXPLORATORY OBJECTIVES: I. To characterize the pharmacokinetics and pharmacodynamics of iberdomide in combination with dinutuximab, cyclophosphamide, topotecan, and GM-CSF. II. To characterize the circulating immune profile of patients treated with and without the addition of iberdomide to the dinutuximab, cyclophosphamide, topotecan, and GM-CSF backbone and explore associations with response to therapy. III. To evaluate associations between GD2 levels in tumor cells from patient bone marrow samples and response to therapy. IV. To collect and bank peripheral blood and tumor tissue (archival and fresh tissue from primary tumor resection or relapse, if available) for future biomarker studies. OUTLINE: This is a phase I, dose-escalation study of iberdomide in combination with cyclophosphamide (CPM), topotecan (Topo), dinutuximab (DIN) and sargramostim (GM-CSF) followed by a phase II study. Patients are assigned to 1 of 2 phases. PHASE 1: Patients receive iberdomide orally (PO), via nasogastric (NG)-tube, or via gastric (G)-tube once daily (QD) on days 1-14 or 1-21, cyclophosphamide intravenously (IV) over 15-30 minutes on days 1-5, topotecan IV over 30 minutes on days 1-5, dinutuximab IV over 10 hours on days 2-5, and sargramostim subcutaneously (SC) or IV over 2 hours starting on day 6 or 7 and continuing for a minimum of 7 doses until absolute neutrophil count (ANC) is ≥ 1500/μL after the expected nadir or until day 21 of each cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. PHASE 2: Patients are randomized to 1 of 2 arms. ARM A: Patients receive cyclophosphamide IV over 15-30 minutes on days 1-5, topotecan IV over 30 minutes on days 1-5, dinutuximab IV over 10 hours on days 2-5, and sargramostim SC or IV over 2 hours starting on day 6 or 7 and continuing for a minimum of 7 doses until ANC is ≥ 1500/μL after the expected nadir or until day 21 of each cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. ARM B: Patients receive iberdomide PO, via NG-tube, or via G-tube QD on days 1-14 or 1-21, as determined in phase 1, cyclophosphamide IV over 15-30 minutes on days 1-5, topotecan IV over 30 minutes on days 1-5, dinutuximab IV over 10 hours on days 2-5, and sargramostim SC or IV over 2 hours starting on day 6 or 7 and continuing for a minimum of 7 doses until ANC is ≥ 1500/μL after the expected nadir or until day 21 of each cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Additionally, all patients undergo echocardiography (ECHO) or multigated acquisition scan (MUGA), bone marrow aspiration and biopsy, computed tomography (CT) or magnetic resonance imaging (MRI), and iobenguane I-123 (123I-MIBG) scans or fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) throughout the study. All patients also undergo blood sample collection on study. After completion of study treatment, patients are followed up at 30 days, 3, 6, and 12 months, every 6 months for years 2-3, and then yearly for years 4-5.
Conditions
- Recurrent Ganglioneuroblastoma
- Recurrent Neuroblastoma
- Refractory Ganglioneuroblastoma
- Refractory Neuroblastoma
Interventions
| Type | Name | Description |
|---|---|---|
| PROCEDURE | Bone Marrow Aspiration | Undergo bone marrow aspiration |
| PROCEDURE | Bone Marrow Biopsy | Undergo bone marrow biopsy |
| PROCEDURE | Computed Tomography | Undergo CT |
| DRUG | Cyclophosphamide | Given IV |
| BIOLOGICAL | Dinutuximab | Given IV |
| PROCEDURE | Echocardiography Test | Undergo ECHO |
| PROCEDURE | FDG-Positron Emission Tomography | Undergo FDG-PET |
| DRUG | Iberdomide | Given PO, NG-tube, or G-tube |
| PROCEDURE | Magnetic Resonance Imaging | Undergo MRI |
| PROCEDURE | Multigated Acquisition Scan | Undergo MUGA |
| RADIATION | Nuclear Radiology Imaging Procedure | Undergo 123I-MIBG scans |
| BIOLOGICAL | Sargramostim | Given SC or IV |
| DRUG | Topotecan | Given IV |
Timeline
- Start date
- 2026-07-30
- Primary completion
- 2029-09-30
- Completion
- 2029-09-30
- First posted
- 2026-02-27
- Last updated
- 2026-04-15
Regulatory
- FDA-regulated drug study
Source: ClinicalTrials.gov record NCT07437963. Inclusion in this directory is not an endorsement.