Recruiting

Phase 1

Phase 2

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

Sponsor:

National Cancer Institute (NCI)

Code:

NCT07437963

Conditions

Recurrent Ganglioneuroblastoma

Recurrent Neuroblastoma

Refractory Ganglioneuroblastoma

Refractory Neuroblastoma

Eligibility Criteria

Sex: All

Age: 1 - 30

Healthy Volunteers: Not accepted

Interventions

Bone Marrow Aspiration

Bone Marrow Biopsy

Computed Tomography

Cyclophosphamide

Dinutuximab

Study Details

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 Ganglioneuroblastoma

Recurrent Neuroblastoma

Refractory Ganglioneuroblastoma

Refractory Neuroblastoma

Study ID

NCT07437963

Start date

Jun 25, 2027

Status verified date

Sep, 2026

Completion date

Sep 30, 2029

Anticipated

Primary completion date

Sep 30, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 1 - 30

Healthy Volunteers: Not accepted

Inclusion Criteria:

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). Patients with stable disease after receiving chemoimmunotherapy for first relapse are not eligible (must be primary refractory disease)
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
Evaluable disease is defined as either:

MIBG-avid lesions only (detected on MIBG scan with positive uptake at minimum of one site that do not meet criteria for measurable disease. This site(s) must represent disease recurrence after completion of therapy, progressive disease on therapy, or refractory disease during induction). OR
New bone site that is avid for FDG-PET (MIBG non-avid tumors) AND has CT/MRI findings consistent with tumor OR has been confirmed by biopsy
Patients with resistant/refractory soft tissue disease that is not MIBG avid or does not demonstrate increased FDG uptake on PET scan must undergo biopsy to document the presence of viable neuroblastoma to be considered a site of disease. Biopsy is not required for patients who have a new site of soft tissue disease or radiographic evidence of disease progression regardless of whether progression occurs while receiving therapy or after completion of therapy

NOTE: Patients with bone marrow only disease are not eligible. Patients with only elevated catecholamines (i.e. > 2 x ULN) are also not eligible for this study
Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2. Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age
For the purposes of this study, "chemoimmunotherapy" is defined as a regimen utilizing any anti-GD2 antibody in combination with cytotoxic chemotherapy, with doses of chemotherapy similar to those used in ANBL1221, ANBL1821, ANBL17P1, ANBL2131, and ANBL19P1
Patient must have received one and NO MORE THAN one prior chemoimmunotherapy-containing regimen

NOTE: Patients who received ANBL2131 Arm B therapy or a similar regimen including anti-GD2 antibody in combination with chemotherapy and then received an extended induction with chemoimmunotherapy (regardless of whether the chemoimmunotherapy was administered for relapse, progression, or poor end of induction response) will be considered to have received two regimens of chemoimmunotherapy. Similarly, patients who receive chemoimmunotherapy during induction or extended induction and then receive chemoimmunotherapy in post-consolidation (e.g., per ANBL19P1) will be considered to have received two regimens of chemoimmunotherapy. These patients are not eligible for this trial
Patient cannot have received more than two prior lines of therapy, including frontline therapy

Standard high-risk induction with or without extended induction followed by consolidation and post-consolidation immunotherapy with or without eflornithine (DFMO) continuation therapy will be considered one line of therapy
ANBL2131 Arm B induction without extended induction followed by consolidation and post-consolidation immunotherapy with or without DFMO continuation therapy will be considered one line of therapy

NOTE: Induction on ANBL2131 Arm B extended induction, and post-consolidation chemoimmunotherapy are each considered separate regimens for the purposes of counting the number of chemoimmunotherapy regimens. In addition, patients who received ANBL2131 Arm B therapy or a similar regimen including anti-GD2 antibody in combination with chemotherapy who received another line of relapse therapy following Arm B or similar treatment are also not eligible
In the relapse setting, one line of therapy will be considered at least one delivered cycle of chemoimmunotherapy (with no limit on the number of consecutive cycles of chemoimmunotherapy)

NOTE: A change in the chemotherapy regimen or anti-GD2 antibody will be considered an additional line of chemoimmunotherapy and these patients will not be eligible for the trial
In the refractory setting where chemoimmunotherapy was used as extended induction or pre-consolidation intensification of therapy for primary refractory disease, one line of therapy will be considered at least 4 delivered cycles of chemoimmunotherapy (with no limit on the number of consecutive cycles of chemoimmunotherapy)

NOTE: A change in the chemotherapy regimen or anti-GD2 antibody will be considered an additional line of chemoimmunotherapy and these patients will not be eligible for the trial
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study
Myelosuppressive chemotherapy: Must not have received within 14 days (2 weeks) of entry onto this study
Biologic (anti-neoplastic agent): Anti-cancer agents not known to be myelosuppressive (e.g. not associated with reduced platelet or ANC counts): ≥ 7 days after the last dose of agent. See Developmental Therapeutics Committee (DVL) homepage for commercial and Phase 1 investigational agent classifications
Antibodies: ≥ 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade ≤ 1
Radiation therapy (RT):

≥ 7 days must have elapsed from small port radiation; ≥ 12 weeks must have elapsed from large field radiation therapy (i.e., total body irradiation, craniospinal, whole abdominal, total lung, > 50% marrow space); ≥ 6 weeks from other substantial bone marrow radiation
Lesions that have been previously radiated cannot be used as target lesions unless there is radiographic evidence of progression at the site following radiation or a biopsy done following radiation shows viable neuroblastoma. Palliative radiation while on study is not permitted
Stem cell transplant (SCT): Patients are eligible ≥ 6 weeks after autologous stem cell transplants or stem cell infusions (including stem cell infusions given as supportive care following iobenguane I-131 \[131I-MIBG\] therapy) as long as hematologic and other eligibility criteria have been met
131I-MIBG therapy: Patients who previously received 131I-MIBG therapy for relapsed/refractory disease or poor end of induction response are not eligible

Prior receipt of 131I-MIBG therapy as part of planned frontline Induction therapy (e.g., ANBL09P1, ANBL1531) is allowed. Patients are eligible ≥ 6 weeks after therapeutic 131I-MIBG provided that all other eligibility criteria are met
Growth factor: Patients must not have received long-acting myeloid growth factors (e.g. pegfilgrastim) within 14 days of entry on this study. Seven days must have elapsed since administration of a short-acting myeloid growth factor or platelet growth factor/stimulating agents (e.g., romiplostim, eltrombopag)
Intravenous immunoglobulin (IVIG): Patients must not have received IVIG within 14 days of study entry
Known HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Peripheral absolute neutrophil count (ANC) ≥ 1000/uL (performed within 7 days prior to enrollment)

Patients known to have bone marrow involvement with neuroblastoma are eligible provided that the minimum ANC and transfusion independent platelet count criteria are met
Platelet count ≥ 100,000/uL (transfusion independent) (performed within 7 days prior to enrollment)

Patients known to have bone marrow involvement with neuroblastoma are eligible provided that the minimum ANC and transfusion independent platelet count criteria are met
A serum creatinine based on age/sex as follows: (performed within 7 days prior to enrollment)

Age: 1 to < 2 years; Maximum serum creatinine (mg/dL): 0.6 (male) 0.6 (female)
Age: 2 to < 6 years; Maximum serum creatinine (mg/dL): 0.8 (male) 0.8 (female)
Age: 6 to < 10 years; Maximum serum creatinine (mg/dL): 1 (male) 1 (female)
Age: 10 to < 13 years; Maximum serum creatinine (mg/dL): 1.2 (male) 1.2 (female)
Age: 13 to < 16 years; Maximum serum creatinine (mg/dL): 1.5 (male) 1.4 (female)
Age: ≥ 16 years; Maximum serum creatinine (mg/dL): 1.7 (male) 1.4 (female) OR - a 24-hour urine creatinine clearance ≥ 60 mL/min/1.73 m\^2 OR - a glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m\^2. If used for eligibility, GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard)
Note: Estimated GFR (eGFR) from serum creatinine, cystatin C or other estimates are not acceptable for determining eligibility
Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age or ≤ 3.0 mg/dL for patients with documented Gilbert's syndrome (performed within 7 days prior to enrollment)
Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) ≤ 135 U/L (performed within 7 days prior to enrollment)

Note: For the purpose of this study, the ULN for SGPT (ALT) has been set to the value of 45 U/L
Shortening fraction of ≥ 27% by echocardiogram (ECHO), OR ejection fraction of ≥ 50% by ECHO or grated radionuclide study (obtained within 21 days prior to enrollment and start of protocol therapy)
No evidence of dyspnea at rest, no exercise intolerance, no chronic oxygen requirement, and room air pulse oximetry > 94% if there is a clinical indication for pulse oximetry. Normal pulmonary function tests in patients who are capable of cooperating with testing (including diffusion capacity of the lung for carbon monoxide \[DLCO\]) are required if there is a clinical indication for determination. For patients who do not have respiratory symptoms, full pulmonary function testing (PFTs) are NOT required (obtained within 21 days prior to enrollment and start of protocol therapy)
Patients with a history of central nervous system (CNS) metastatic disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment. Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled
CNS toxicity ≤ grade 2

Exclusion Criteria:

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 sargramostim (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, naxitamab-gqgk, or sargramostim (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 with a significant intercurrent illness (any ongoing serious medical problem unrelated to cancer or its treatment) that is not covered by the detailed exclusion criteria and that is expected to interfere with the action of study agents or to significantly increase the severity of the toxicities experienced from study treatment are not eligible
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
Female patients who are pregnant are not eligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs. Pregnancy tests and monthly counseling are required for individuals of childbearing potential. Male patients must practice complete abstinence or agree to use a condom during sexual contact with individuals of childbearing potential (IOCBP) while participating in the study, during dose interruptions, and for at least 28 days following discontinuation from the study, even if he has undergone a successful vasectomy
Lactating females who plan to breastfeed their infants are not eligible
Sexually active patients of reproductive potential who have not agreed to use two effective methods of contraception simultaneously without interruption, for at least 7 days before starting study treatment, throughout the entire duration of study treatment, during dose interruptions, and for at least 28 days after the last dose of iberdomide are not eligible. The two methods of contraception must include one highly effective method and one additional effective method
All patients and/or their parents or legal guardians must sign a written informed consent
All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Study Design

Enrollment

76 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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.

active comparator: Phase 2 arm A (CPM, Topo, DIN, GM-CSF)

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.

experimental: Phase 2 arm B (iberdomide, CPM, Topo, DIN, GM-CSF)

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.

Interventions

Bone Marrow Aspiration

Undergo bone marrow aspiration

Bone Marrow Biopsy

Undergo bone marrow biopsy

Computed Tomography

Undergo CT

Cyclophosphamide

Given IV

Dinutuximab

Given IV

Echocardiography Test

Undergo ECHO

FDG-Positron Emission Tomography

Undergo FDG-PET

Iberdomide

Given PO, NG-tube, or G-tube

Magnetic Resonance Imaging

Undergo MRI

Multigated Acquisition Scan

Undergo MUGA

Nuclear Radiology Imaging Procedure

Undergo 123I-MIBG scans

Sargramostim

Given SC or IV

Topotecan

Given IV

Primary outcome measure

Incidence of therapy-associated dose limiting toxicities (Phase 1) [ Time Frame: During cycle 1 (Cycle length = 28 days) ]
Recommended phase 2 dose (Phase 1) [ Time Frame: Up to the completion of phase 1 ]
Proportion of eligible patients who are responders (Phase 2) [ Time Frame: Post-randomization up through the end of cycle 12 (Cycle length = 28 days) ]

Central Contacts and Locations

Locations

Children's Oncology Group

Recruiting

Oakland, California, United States, 94607

Contacts

Kieuhoa T. Vo

kieuhoa.vo@ucsf.edu

Principal Investigator:

Kieuhoa T. Vo

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Oct 16, 2026

Last verified

Sep, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-17. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-10-16. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.