Testing the Addition of Iberdomide to Therapy in People With Neuroblastoma That Has Come Back, Not Responded to Treatment, or Gotten Worse

NCT07437963 | Not Yet Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2026-01050ANBL2421U10CA180886
• Study Type: interventional
• Target: 76
• Locations: 0 countries
• Sites: N/A

Brief 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.

Conditions

Recurrent Neuroblastoma; Refractory Neuroblastoma; Recurrent Ganglioneuroblastoma; Refractory Ganglioneuroblastoma

Outcome Measures

Primary Outcomes (3)

• Incidence of therapy-associated dose limiting toxicities (Phase 1)

  Graded using Common Terminology Criteria for Adverse Events version 5.0.

  During cycle 1 (Cycle length = 28 days)

• Recommended phase 2 dose (Phase 1)

  Will be assessed by determining the recommended phase 2 dose of iberdomide administered in combination with dinutuximab, cyclophosphamide, topotecan, and granulocyte-macrophage colony-stimulating factor (GM-CSF) using the rolling six design.

  Up to the completion of phase 1

• Proportion of eligible patients who are responders (Phase 2)

  Responders are defined as patients who achieve a minor response (MR) or better, per the revised International Neuroblastoma Response Criteria (INRC), as their best overall response at any time post-randomization up through the end of cycle 12. Will be evaluated by Boschloo's test to compare the response rates in the two arms, and the futility monitoring rules. The response rate by the end of 12 cycles as determined by central review will be calculated in each arm, including placement of a 95% confidence interval (CI). If the response rate on Arm B is significantly better, then it will be considered a therapeutic regimen worthy of further testing in patients with high-risk neuroblastoma. In addition, the rate of complete response + partial response by the end of 12 cycles as determined by central review will be calculated in each arm, including placement of a 95% CI, as well as response within each of the INRC components.

  Post-randomization up through the end of cycle 12 (Cycle length = 28 days)

Secondary Outcomes (5)

• Response rate (Phase 1)

  Up to 12 cycles (Cycle length = 28 days)

• Progression-free survival (Phase 2)

  From the time of randomization to the occurrence of relapse, progressive disease, or death, assessed up to 5 years

• Overall survival (Phase 2)

  From the time of randomization to death, assessed up to 5 years

• Duration of response

  From randomization to disease progression or death in eligible patients, except those placed off study due to lack of insurance coverage, who achieve a MR or better, assessed up to 5 years

• Incidence of grade ≥ 3 toxicities (Phase 2 Arm B)

  Up to 5 years post-treatment

Other Outcomes (4)

• Pharmacokinetic (PK) parameters of iberdomide in combination with dinutuximab, cyclophosphamide, topotecan, and GM-CSF

  Cycle (C) 1 day (D) 1, C1D2, and C1D8, 9, or 10 (Phase 1 patients) and C1D8, C2D8, and C3D8 (Phase 2 patients) (Cycle length = 28 days)

• Pharmacodynamic (PD) parameters of iberdomide in combination with dinutuximab, cyclophosphamide, topotecan, and GM-CSF (Phase 1)

  C1D1 and C1D2 (Cycle length = 28 days)

• Immune profiling results (Phase 2)

  C1D1, C1D15 or 22, C2D1, C3D1, and at progression (Cycle length = 28 days)

Study Arms (3)

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF)

EXPERIMENTAL

Patients receive iberdomide PO, via NG-tube, or via G-tube QD on days 1-14 or 1-21, 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, patients undergo ECHO or MUGA, bone marrow aspiration and biopsy, CT or MRI, and 123I-MIBG scans or FDG-PET throughout the study. Patients also undergo blood sample collection on study.

Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Biological: Dinutuximab; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Drug: Iberdomide; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Radiation: Nuclear Radiology Imaging Procedure; Biological: Sargramostim; Drug: Topotecan

Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF)

EXPERIMENTAL

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, patients undergo ECHO or MUGA, bone marrow aspiration and biopsy, CT or MRI, and 123I-MIBG scans or FDG-PET throughout the study. Patients also undergo blood sample collection on study.

Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Biological: Dinutuximab; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Drug: Iberdomide; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Radiation: Nuclear Radiology Imaging Procedure; Biological: Sargramostim; Drug: Topotecan

Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

ACTIVE COMPARATOR

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. Additionally, patients undergo ECHO or MUGA, bone marrow aspiration and biopsy, CT or MRI, and 123I-MIBG scans or FDG-PET throughout the study. Patients also undergo blood sample collection on study.

Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Computed Tomography; Drug: Cyclophosphamide; Biological: Dinutuximab; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Radiation: Nuclear Radiology Imaging Procedure; Biological: Sargramostim; Drug: Topotecan

Interventions

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Dinutuximab BIOLOGICAL

Given IV

Also known as: Ch 14.18UTC, Ch14.18, Dinutuximab Beta, MOAB Ch14.18, monoclonal antibody Ch14.18, Qarziba, Unituxin

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

FDG-Positron Emission Tomography PROCEDURE

Undergo FDG-PET

Also known as: FDG, FDG-PET, FDG-PET Imaging

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Iberdomide DRUG

Given PO, NG-tube, or G-tube

Also known as: CC 220, CC-220

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Nuclear Radiology Imaging Procedure RADIATION

Undergo 123I-MIBG scans

Also known as: NUCLEAR RADIOLOGY

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Sargramostim BIOLOGICAL

Given SC or IV

Also known as: 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine, rhu GM-CFS, Sagramostim, Sargramostatin

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Topotecan DRUG

Given IV

Also known as: Hycamptamine, Topotecan Lactone

Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 1 arm b (iberdomide, CPM, Topo, DIN, GM-CSF); Phase 2 arm a (CPM, Topo, DIN, GM-CSF)

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Patients must be ≥ 1 year of age and ≤ 30 years of age at the time of study enrollment
• Patients must have had histologic verification of neuroblastoma or ganglioneuroblastoma or demonstration of neuroblastoma cells in the bone marrow with elevated urinary catecholamines (i.e. \> 2 x upper limit of normal \[ULN\]), at the time of initial diagnosis
• Progressive/relapsed or refractory (defined as persistent disease with overall response no better than minor response \[MR\] to prior therapy per revised International Neuroblastoma Response Criteria \[INRC\]) neuroblastoma based on the revised INRC
• Patients must meet ONE of the following criteria:
• Primary refractory disease
• Primary refractory disease following chemoimmunotherapy as part of induction therapy (e.g., ANBL17P1, ANBL2131 Arm B). Patients with primary refractory disease must have received at least 4 cycles of frontline high-risk induction chemoimmunotherapy
• Primary refractory disease following aggressive multi-drug induction chemotherapy on or according to a high-risk NB protocol (e.g., A3973, ANBL0532, ANBL09P1, ANBL12P1, ANBL1531, or ANBL2131 Arm A) with persistent disease at the conclusion of at least 4 cycles of chemoimmunotherapy used as extended induction or pre-consolidation intensification of therapy for primary refractory disease (e.g., ANBL2131 Arm A with extended induction, ANBL1221, or ANBL1821)
• NOTE: Patients who experienced disease progression either during or within 30 days of completion (last day of anti-GD2 antibody) of chemoimmunotherapy during induction or extended induction are not eligible for the study
• Relapsed/progressive disease
• First episode of recurrence following chemoimmunotherapy as part of induction therapy (e.g., ANBL17P1, ANBL2131 Arm B) or extended induction (e.g., ANBL2131 Arm A)
• NOTE: Patients who experienced disease progression either during or within 30 days of completion (last day of anti-GD2 antibody) of chemoimmunotherapy during induction or extended induction are not eligible for the study
• First episode of recurrent/progressive disease detected during or following chemoimmunotherapy used as part of post-consolidation therapy (e.g., ANBL19P1)
• Second episode of recurrent/progressive disease detected during or following chemoimmunotherapy used as first-line salvage therapy for recurrent or progressive disease (e.g., ANBL1221, ANBL1821)
• Evaluable or measurable disease per the revised INRC
• Measurable soft tissue disease per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 that is metaiodobenzylguanidine (MIBG) avid or demonstrates increased FDG uptake on PET scan

You may not qualify if:

• Patients who received allogeneic stem cell therapy will be excluded
• Patients must have been off pharmacologic doses of systemic steroids for at least 7 days prior to enrollment. Patients who require or are likely to require pharmacologic doses of systemic corticosteroids while receiving treatment on this study are ineligible. The only exception is for patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration in order to avoid allergic transfusion reactions. The use of conventional doses of inhaled steroids for the treatment of asthma is permitted, as is the use of physiologic doses of steroids for patients with known adrenal insufficiency. Patients on any other immunosuppressive medications (e.g. cyclosporine, tacrolimus) are not eligible
• Patients with untreated CNS disease will be excluded. If the CNS disease has been adequately treated (e.g., surgical resection and radiation; or radiation alone) and there is no evidence of progression in the CNS, then the patient will be eligible
• Patients with a history of having to permanently discontinue anti-GD2 therapy or sargarmostim (GM-CSF) due to drug-related toxicity will be excluded
• Patients with a history of grade 4 allergic reactions or other drug-related toxicities that required permanent discontinuation of dinutuximab, dinutuximab-beta, or sargarmostim (GM-CSF) will be excluded
• Patients with myelodysplastic syndrome or with any other malignancy other than neuroblastoma will be excluded
• Patients with prior exposure to iberdomide will be excluded
• Patients with a history of serious allergic reaction to another immunomodulatory agent (e.g., thalidomide, lenalidomide, or pomalidomide) will be excluded
• Patients who are unable to tolerate oral/nasogastric/gastrostomy medications will not be eligible for this trial. Additionally, patients with significant malabsorption such as chronic gastrointestinal diseases (e.g., inflammatory bowel disease) or significant bowel resection that would preclude adequate oral medication absorption will be excluded
• Patients must not have received enzyme-inducing anticonvulsants including but not limited to phenytoin, phenobarbital, or carbamazepine for at least 7 days prior to study enrollment. Patients receiving non-enzyme inducing anticonvulsants such as gabapentin, valproic acid, or levetiracetam will be eligible
• Patients who have received drugs that are strong inducers or inhibitors of CYP3A4 within 14 days prior to study enrollment are not eligible
• Patients with history of prior unprovoked thrombosis/thromboembolic events are not eligible. Patients with a history of provoked thrombosis/thromboembolic events (e.g., related to central lines) are eligible if they no longer require anti-coagulation or have been on a stable dose of anticoagulation therapy for at least 6 weeks before the first dose of study treatment and have no complications from the thrombosis/thromboembolic event or the anticoagulation regimen
• Patients who have an uncontrolled infection are not eligible
• Patients with peripheral neuropathy ≥ grade 2 are excluded
• Patients who experienced disease progression either during or within 30 days of completion of chemoimmunotherapy during induction or extended induction are not eligible for the study

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Ganglioneuroblastoma; Neuroblastoma

Interventions

Biopsy; Cyclophosphamide; dinutuximab; iberdomide; Magnetic Resonance Spectroscopy; sargramostim; Colony-Stimulating Factors; Topotecan

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Spectrum Analysis; Chemistry Techniques, Analytical; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Camptothecin; Alkaloids; Heterocyclic Compounds

Study Officials

• Kieuhoa T Vo

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Model Details: Phase 1: Dose escalation and determination of RP2D. Randomized Phase 2: The RP2D of iberdomide established in Phase 1 will be used as the treatment dose in Phase 2.

Study Record Dates

• First Submitted: February 26, 2026
• First Posted: February 27, 2026
• Study Start (Estimated): July 30, 2026
• Primary Completion (Estimated): September 30, 2029
• Study Completion (Estimated): September 30, 2029
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share