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Retinoid

Isotretinoin +/- Immunotherapy for Neuroblastoma

Phase 3

Waitlist Available

Led By Alice L Yu

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

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

Must have

All patients must have completed therapy including intensive induction followed by ASCT and radiotherapy to be eligible for ANBL0032; radiotherapy may be waived for patients who either have small adrenal masses which are completely resected up front, or who never have an identifiable primary tumor; examples of such therapies include: Following treatment per A3973 protocol, Following treatment per Pediatric Oncology Group (POG)-9341/9342 protocol, Following treatment per CCG3891, Following treatment on New Approaches to Neuroblastoma Therapy (NANT) 2001-02, Enrollment on or following treatment per ANBL02P1, Enrollment on or following treatment per ANBL07P1

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 10 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial will compare isotretinoin alone to isotretinoin with dinutuximab, aldesleukin, and sargramostim following stem cell transplant in treating patients with neuroblastoma.

Who is the study for?

This trial is for patients with high-risk neuroblastoma who have completed intensive induction, stem cell transplant, and radiotherapy. Eligible participants must not have had prior anti-GD2 antibody therapy, should be able to perform daily activities at least half of the time (>=50% performance score), expect to live more than 2 months, and have adequate organ function. They must also agree to use birth control if applicable and cannot be breastfeeding.

What is being tested?

The study tests whether adding dinutuximab (a monoclonal antibody), aldesleukin (stimulates white blood cells), and sargramostim (boosts immune system) to isotretinoin chemotherapy improves outcomes in neuroblastoma post-stem cell transplant compared to isotretinoin alone. It's a phase III trial where some patients are randomly chosen to receive the additional drugs.

What are the potential side effects?

Possible side effects include reactions related to the immune system such as inflammation or allergy-like symptoms due to dinutuximab; fatigue; changes in blood pressure or heart rate from aldesleukin; bone pain or fever from sargramostim; dry skin or lips, nosebleeds, joint pains from isotretinoin.

Eligibility Criteria

Inclusion Criteria

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

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I completed therapy for my cancer, including intensive treatment and a stem cell transplant.

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I've completed therapy for neuroblastoma, including intensive treatments and possibly surgery.

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My kidney function is within the required range for my age and gender.

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My lung function tests are above 60% of what's expected, or I'm a child without breathing issues.

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I have never received GD2 antibody therapy.

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I can do most activities and my doctor thinks I have at least 2 months to live.

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My kidney function is normal or near normal.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 10 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 10 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 10 years for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

Event-Free Survival (EFS)

Event-Free Survival (EFS) of Patients From the Non-randomized Portion of the Trial

Incidence of Toxicities Assessed Using Common Terminology Criteria for Adverse Events Version 4.0

+3 more

Other study objectives

Average Level of HACA

Cardiac Repolarization

Change in MRD

+8 more

Side effects data

From 2021 Phase 1 & 2 trial • 24 Patients • NCT03010358

33%

Infusion Related Reaction

33%

Alanine aminotransferase increased

33%

Aspartate aminotransferase increased

33%

Neutrophil count decreased

17%

Sinusitis

17%

Tumor Lysis Syndrome

17%

Interoperative Hemorrhage

17%

Platelet count decreased

17%

Febrile neutropenia

17%

Infusion related reaction

17%

Upper respiratory infection

17%

Otitis externa

100%

80%

60%

40%

20%

Study treatment Arm

Phase 1, Dose 1 (400 mg Entospletinib Daily)

Phase 2 and MTD (800 mg Entospletinib Daily)

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm II (sargramostim, dinutuximab, aldesleukin, isotretinoin)Experimental Treatment7 Interventions

Beginning preferably between day 56 and day 85 post-ASCT, but may be delayed up to day 200, patients receive immunotherapy comprising sargramostim SC or IV over 2 hours on days 0-13 during courses 1, 3, and 5 and dinutuximab IV over 10-20 hours on days 3-6 of courses 1-5. Patients also receive aldesleukin IV continuously on days 0-3 and 7-10 during courses 2 and 4. Immunotherapy repeats every 28 days for 5 courses in the absence of disease progression or unacceptable toxicity. Patients also receive isotretinoin as in Arm I beginning on day 11 of immunotherapy.

Group II: Arm I (isotretinoin) (closed to accrual as of 4/16/2009)Active Control4 Interventions

Beginning preferably between day 56 and day 85 post-ASCT, but may be delayed up to day 200, patients receive isotretinoin PO BID for 14 days. Treatment repeats every 28 days for 6 courses in the absence of disease progression or unacceptable toxicity. Patients may cross over to Arm II provided they have not experienced disease progression and have not received any further anti-neuroblastoma therapy following completion of isotretinoin therapy.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Aldesleukin

2012

Completed Phase 4

~1610

Dinutuximab

2009

Completed Phase 3

~710