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AzTrials

Recurrent GanglioneuroblastomaPhase 1/2NCT07437963

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

A Phase 1/2 study testing Bone Marrow Aspiration, Bone Marrow Biopsy and Computed Tomography in people with Recurrent Ganglioneuroblastoma and Recurrent Neuroblastoma, run by National Cancer Institute (NCI) at 4 sites in United States.

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Trial 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… Read more about this study

Who is it for?
Ages 1 year to 30 years
What is being tested?
Bone Marrow Aspiration, Bone Marrow Biopsy and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
76 participants
Where
4 sitesUnited States
Study dates
25 Jun 2027to 30 Sep 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

4 sites in 1 country. Contact the study team or a site near you to ask about taking part.

United States4 sites, 4 recruiting

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

    Site Public Contact, 773-880-4562

    Elizabeth A. Sokol

    Recruiting

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

    Site Public Contact, 864-522-4317, Kim.Williams3@prismahealth.org

    Stuart L. Cramer

    Recruiting

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

    Site Public Contact, 212-639-7592

    Fiorella Iglesias

    Recruiting

  • Children's Oncology Group

    Oakland, California, 94607

    Kieuhoa T. Vo, kieuhoa.vo@ucsf.edu

    Kieuhoa T. Vo

    Recruiting

Other trials in United States

About this study

Official title: 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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Bone Marrow Aspiration, Bone Marrow Biopsy, Computed Tomography, Cyclophosphamide, Dinutuximab
Medical subject headings
Ganglioneuroblastoma, Neuroblastoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Bone Marrow BiopsyProcedure or surgery

    Also called Biopsy of Bone Marrow, Biopsy, Bone Marrow

    Undergo bone marrow biopsy

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518

    Given IV

  • DinutuximabBiological

    Also called Ch 14.18UTC, Ch14.18, Dinutuximab Beta, MOAB Ch14.18

    Given IV

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • FDG-Positron Emission TomographyProcedure or surgery

    Also called FDG, FDG-PET, FDG-PET Imaging

    Undergo FDG-PET

  • IberdomideDrug

    Also called CC 220, CC-220, Zenbexus

    Given PO, NG-tube, or G-tube

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • Nuclear Radiology Imaging ProcedureRadiation

    Also called NUCLEAR RADIOLOGY

    Undergo 123I-MIBG scans

  • SargramostimBiological

    Also called 23-L-Leucinecolony-Stimulating Factor 2, DRG-0012, Leukine, Prokine

    Given SC or IV

  • TopotecanDrug

    Also called Hycamptamine, Topotecan Lactone

    Given IV

Study groups in NCT07437963
Study groupRoleWhat they receive
Phase 1 (iberdomide, CPM, Topo, DIN, GM-CSF)ExperimentalPatients 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.
Receives: 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 comparatorPatients 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.
Receives: 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
Phase 2 arm B (iberdomide, CPM, Topo, DIN, GM-CSF)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to the completion of phase 1

  2. Response rate (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 through the end of cycle 12. The response rate by the end of 12 cycles as determined by central review will be calculated, including placement of a 95% confidence interval.

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

Secondary outcomes (5)

  1. Response rate (Phase 1)

    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 through the end of cycle 12. The response rate by the end of 12 cycles as determined by the institution will be calculated, including placement of a 95% confidence interval.

    Measured: Up to 12 cycles (Cycle length = 28 days)

  2. Progression-free survival (Phase 2)

    Kaplan-Meier method will be used to estimate progression-free survival (PFS). PFS time will be calculated from the time of randomization to the occurrence of relapse, progressive disease, or death. Patients without a PFS event will be censored at the time of last follow-up. 1-Year PFS is provided.

    Measured: Up to 1 year

  3. Overall survival (Phase 2)

    Kaplan-Meier method will be used to estimate overall survival (OS). OS time will be calculated from the time of randomization to the occurrence of death. Patients still alive will be censored at the time of last follow-up.1-Year OS is provided.

    Measured: Up to 1 year

  4. Confirmed response rate (Phase 2)

    A confirmed response is defined as a minor response (MR) or better that is confirmed by a second disease evaluation obtained at least 4 weeks after first documentation of MR or better. The confirmed response rate will be provided.

    Measured: Up to 12 cycles (Cycle length = 28 days)

  5. Duration of response (Phase 2)

    Duration of response will be calculated as the time from first achievement of response to disease progression or death in patients who achieve a minor response (MR) or better. Duration of response will be provided.

    Measured: Up to 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Feb 2026
  2. Study start25 Jun 2027 (estimated)
  3. Primary completion30 Sep 2029 (estimated)
  4. Study completion30 Sep 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
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.
Masking
None (open label)
Enrolment
76 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07437963
Sponsor's protocol ID
NCI-2026-01050
Other IDs
NCI-2026-01050, ANBL2421, ANBL2421, U10CA180886
Status last verified
Oct 2026
First submitted
26 Feb 2026
Last updated
6 Nov 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Bone Marrow Aspiration, Bone Marrow Biopsy and Computed Tomography in people with Recurrent Ganglioneuroblastoma and Recurrent Neuroblastoma, run by National Cancer Institute (NCI) at 4 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 64 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Recommended phase 2 dose (Phase 1) (time frame: Up to the completion of phase 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07437963.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.

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