What side effects are associated with this type of intervention?

Common treatments for neuroblastoma, such as 131I-Metaiodobenzylguanidine (131I-MIBG) and Dinutuximab, have several known side effects. 131I-MIBG therapy can cause hematologic toxicity, including thrombocytopenia and neutropenia, as well as potential thyroid dysfunction and secondary malignancies. Dinutuximab, a monoclonal antibody targeting GD2, is associated with neuropathic pain, infusion reactions, capillary leak syndrome, and hypotension. High-dose chemotherapy and autologous stem cell transplantation, often used in conjunction, can lead to severe myelosuppression, increased risk of infections, and organ toxicity. These treatments require careful monitoring and supportive care to manage adverse effects.

What prior FDA approvals exist?

The FDA has approved several treatments for neuroblastoma, particularly those targeting neuroblastoma cells with radiopharmaceuticals and monoclonal antibodies. 131I-Metaiodobenzylguanidine (131I-MIBG) is a radiopharmaceutical that targets neuroblastoma cells and has been used effectively in treating refractory or relapsed neuroblastoma. Dinutuximab, a monoclonal antibody targeting the GD2 antigen on neuroblastoma cells, has also been approved and is used in combination with other therapies to improve outcomes in high-risk neuroblastoma patients. These treatments represent significant advancements in targeting and managing neuroblastoma.

What other types of research exist?

Promising novel alternatives for neuroblastoma treatment include: <ol> <li>CAR T-cell therapy targeting GD2, which has shown potential in early-phase clinical trials.</li> <li></li> </ol> ALK inhibitors like Lorlatinib for patients with ALK-mutated neuroblastoma. 3. Anti-PD1/PDL1 therapies such as Nivolumab and Pembrolizumab, which are being explored for their efficacy in neuroblastoma. 4. Combination therapies involving targeted agents like Crizotinib with conventional chemotherapy. 5. Novel radiopharmaceuticals like 177Lu-DOTATATE, which target somatostatin receptors expressed in some neuroblastomas.

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Radiopharmaceutical

MIBG + Dinutuximab Therapy for Neuroblastoma

Phase 1

Waitlist Available

Research Sponsored by New Approaches to Neuroblastoma Therapy Consortium

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines

All patients must have at least one of the following: Recurrent/progressive disease after the diagnosis of high-risk neuroblastoma at any time prior to enrollment regardless of response to frontline therapy, refractory disease with a best overall response of no response/stable disease since diagnosis of high-risk neuroblastoma and at least 4 cycles of induction therapy, persistent disease with a best overall response of no partial response since diagnosis of high-risk neuroblastoma and at least 4 cycles of induction therapy

Must not have

Patients who are on hemodialysis

Patient declines participation in NANT 2004-05, the NANT Biology Study

Timeline

Screening 3 weeks

Treatment Varies

Follow Up all toxicities from enrollment until completion of course 1 (day 56)

Awards & highlights

All Individual Drugs Already Approved

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial tests a combination of a radioactive drug, an antibody, and possibly another drug in children with hard-to-treat neuroblastoma. The treatment works by killing cancer cells directly and helping the immune system attack them.

Who is the study for?

This trial is for pediatric patients with high-risk neuroblastoma, a type of cancer. They must have evidence of MIBG uptake in tumors or increased urinary catecholamines and meet specific criteria regarding their disease state (recurrent/progressive, refractory, persistent). Participants need to be recovered from prior treatments and have adequate organ function. Pregnant individuals or those unable to follow the study plan are excluded.

What is being tested?

The trial tests a combination therapy using 131I-MIBG with dinutuximab for children with neuroblastoma that's resistant or has come back after treatment. If safe, vorinostat will be added at a certain dose level. The study uses a 'rolling 6' design to find the best dose for phase 2 trials and includes additional patient groups to confirm findings.

What are the potential side effects?

Possible side effects include reactions related to immune system activation by dinutuximab such as pain, fever, allergic responses; thyroid issues due to potassium iodide; blood cell changes from sargramostim; and fatigue or digestive problems from vorinostat.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have been diagnosed with neuroblastoma confirmed by tests.

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My high-risk neuroblastoma has not improved after initial treatments.

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I have a lesion from neuroblastoma or ganglioneuroblastoma that can't be measured but was confirmed by biopsy or is MIBG avid.

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I am expected to live at least 12 weeks and can do some daily activities on my own.

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I have recovered from side effects of my previous cancer treatments.

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I have a tumor that can be measured and fits specific size criteria.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently receiving hemodialysis.

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I have chosen not to participate in the NANT 2004-05 study.

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I have never stopped anti-GD2 therapy because of side effects.

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I have never had total body irradiation.

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I have had a stem cell transplant from a donor.

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I have a history of HIV, hepatitis B, or hepatitis C.

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My major organs are healthy enough to handle treatment.

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I have been treated with an HDAC inhibitor and 131I-MIBG together.

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I do not have any ongoing or uncontrolled infections.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ all toxicities from enrollment until completion of course 1 (day 56)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~all toxicities from enrollment until completion of course 1 (day 56)

This trial's timeline: 3 weeks for screening, Varies for treatment, and all toxicities from enrollment until completion of course 1 (day 56) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Describe Non Hematological Toxicities Cohort B

Describe Non-Hematological Toxicities Cohort A

MTD/RP2D determination Cohort A

+1 more

Secondary study objectives

Overall Response Cohort A

Overall Response Cohort B

Side effects data

From 2021 Phase 2 trial • 114 Patients • NCT02035137

92%

10035528-Platelet count decreased

86%

10002272-Anemia

84%

10029366-Neutrophil count decreased

81%

10049182-White blood cell decreased

76%

10025256-Lymphocyte count decreased

57%

10003481-Aspartate aminotransferase increased

54%

10047700-Vomiting

46%

10001551-Alanine aminotransferase increased

43%

10000636-Activated partial thromboplastin time prolonged

38%

10002646-Anorexia

35%

10021038-Hyponatremia

35%

10028813-Nausea

32%

10016256-Fatigue

30%

10020943-Hypoalbuminemia

30%

10011224-Cough

27%

10016558-Fever

27%

10020639-Hyperglycemia

27%

10021018-Hypokalemia

22%

10012727-Diarrhea

22%

10020949-Hypocalcemia

22%

10021059-Hypophosphatemia

19%

10010774-Constipation

19%

10020670-Hypermagnesemia

16%

10028735-Nasal congestion

16%

10022402-INR increased

14%

10047900-Weight loss

14%

10001675-Alkaline phosphatase increased

14%

10019211-Headache

14%

10040752-Sinus tachycardia

11%

10011368-Creatinine increased

11%

10006504-Bruising

11%

10021097-Hypotension

11%

10021028-Hypomagnesemia

11%

10033371-Pain

10020772-Hypertension

10002855-Anxiety

10013781-Dry mouth

10005364-Blood bilirubin increased

10014383-Electrocardiogram QT corrected interval prolonged

10003988-Back pain

10000081-Abdominal pain

10001760-Alopecia

10020680-Hypernatremia

10034310-Penile pain

10014222-Edema face

10033425-Pain in extremity

10041367-Sore throat

10001723-Allergic rhinitis

10012174-Dehydration

10025482-Malaise

10000060-Abdominal distension

10045158-Tumor pain

10021005-Hypoglycemia

10020647-Hyperkalemia

10028130-Mucositis oral

10021143-Hypoxia

10056910-GGT increased

10001497-Agitation

10062501-Non-cardiac chest pain

INFLUENZA A

10017577-Gait disturbance

10016791-Flu like symptoms

10009887-Colitis

10016825-Flushing

10007810-Catheter related infection

10008531-Chills

10031009-Oral pain

10041349-Somnolence

10013573-Dizziness

10017076-Fracture

RESPIRATORY DEPRESSION FROM SEDATION

10046300-Upper respiratory infection

10040047-Sepsis

10065764-Mucosal infection

10008496-Chest wall pain

10033987-Paresthesia

10037032-Proteinuria

RIB PAIN

10013911-Dysgeusia

10038695-Respiratory failure

MURMUR

URETHRAL TRAUMA

10035598-Pleural effusion

10016059-Facial pain

10046555-Urinary retention

10054482-Neck edema

10037868-Rash maculo-papular

DRY CRACKED LIPS

HYPERPHOSPHATEMIA

10041232-Sneezing

10065780-Muscle weakness left-sided

10049737-Treatment related secondary malignancy

10020587-Hypercalcemia

10050068-Edema limbs

10051792-Infusion related reaction

10015090-Epistaxis

10013963-Dyspnea

JAW PAIN

10021114-Hypothyroidism

MULTIPLE BACTERIAL INFECTIONS (ENTEROBACTER, CITROBACTER, KLEBSIELLA, GPC, GVC)

10025258-Lymphocyte count increased

10019450-Hematuria

10019245-Hearing impaired

10028836-Neck pain

ENTEROBACTER CLOCACAE

10061322-Optic nerve disorder

10065776-Muscle weakness lower limb

DISEASE PROGRESSION

10030980-Oral hemorrhage

100%

80%

60%

40%

20%

Study treatment Arm

131I-MIBG With Vorinostat

131I-MIBG With Vincristine/Irinotecan

Single-Agent 131I-MIBG

Awards & Highlights

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 other conditions.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: 131I-MIBG with Dinutuximab and VorinostatExperimental Treatment5 Interventions

Patients will receive vorinostat on days 0-13. 131I-MIBG will be received on day 1. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab and 131I-MIBG dose will be based on the dose level assigned at the time of patient registration. 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

Group II: 131I-MIBG with DinutuximabExperimental Treatment4 Interventions

Patients will receive 131I-MIBG on day 1. Dinutuximab is given intravenously on days 8-11 and 29-32 of therapy. Dinutuximab and 131I-MIBG dose will be based on the dose level assigned at the time of patient registration. 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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Potassium Iodide

FDA approved

131I-MIBG

2005

Completed Phase 2

~220

Dinutuximab

FDA approved

Vorinostat

2014

Completed Phase 3

~1600

Sargramostim

FDA approved

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

131I-Metaiodobenzylguanidine (131I-MIBG) is a radiopharmaceutical that targets neuroblastoma cells by mimicking norepinephrine, which is taken up by neuroblastoma cells due to their high expression of norepinephrine transporters. Once inside the cells, the radioactive iodine delivers targeted radiation, causing cell death. Dinutuximab is a monoclonal antibody that targets GD2, a disialoganglioside highly expressed on neuroblastoma cells. By binding to GD2, Dinutuximab marks the cancer cells for destruction by the immune system. These treatments are significant for Neuroblastoma patients as they offer targeted approaches that can specifically attack cancer cells while minimizing damage to normal tissues, potentially improving outcomes and reducing side effects.