Lenalidomide and Dinutuximab With or Without Isotretinoin in Treating Younger Patients With Refractory or Recurrent Neuroblastoma

NCT01711554 | Active Not Recruiting Phase 1

• 6 other identifiers: NCI-2012-02011CDR0000741991N2011-04NANT 11-04NANT N2011-04P01CA081403
• Study Type: interventional
• Target: 27
• Locations: 2 countries
• Sites: 15

Brief Summary

This phase I trial studies the side effects and best dose of lenalidomide when given together with dinutuximab with or without isotretinoin in treating younger patients with neuroblastoma that does not respond to treatment or that has come back. Drugs used in chemotherapy, such as lenalidomide and isotretinoin, 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. Monoclonal antibodies, such as dinutuximab, may interfere with the ability of tumor cells to grow and spread. Giving more than one drug (combination chemotherapy) together with dinutuximab therapy may kill more tumor cells.

Conditions

Refractory Neuroblastoma; Recurrent Neuroblastoma

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose defined as the highest dose level tested at which 0/6 or 1/6 patients experience dose-limiting toxicity (DLT) graded using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) criteria, version 4.0

  All toxicities observed will be summarized in terms of type (organ affected or laboratory determination), severity (by NCI CTCAE), and attribution. Tables will be created to summarize these toxicities and side effects by dose level and by course as well as with Kaplan-Meier plots (i.e. time to first delay or dose reduction) in order to assess the tolerability of the regime over multiple courses.

  Up to 28 days

• Recommended phase II dose

  Determination of the recommended phase II dose of lenalidomide will include consideration of obtaining median peak plasma lenalidomide levels of 5-10 uM (based on laboratory modeling of this regimen in neuroblastoma), acceptable clinical toxicity, and laboratory evidence of an augmentation in immune function.

  Up to 28 days

Secondary Outcomes (7)

• Overall survival

  From start of lenalidomide until death for any reason or date that patient was last known to be alive if the patient is still alive, assessed up to 3 years

• Event-free survival

  From the start of treatment with lenalidomide until progression, clinical deterioration mandating that the patient terminate treatment or death due to any cause, whichever occurs first, assessed up to 3 years

• Changes in the levels of T cells, natural killer (NK) cells, monocytes, cytokines, and chemokines

  Baseline to up to 28 days

• Changes in levels of HACA (or other genotype) and tumor response

  Baseline to up to 3 years

• Pharmacokinetic determinations of lenalidomide

  Baseline, at 60 and 90 minutes, at 2, 6, 24 hours and days 7 and 22 after last dose of lenalidomide in course 1

Study Arms (1)

Treatment (lenalidomide, dinutuximab, isotretinoin)

EXPERIMENTAL

Patients receive lenalidomide PO QD on days 1-21, dinutuximab IV over 10 hours on days 8-11, and isotretinoin PO BID on days 15-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.

Biological: Dinutuximab; Drug: Isotretinoin; Other: Laboratory Biomarker Analysis; Drug: Lenalidomide; Other: Pharmacological Study

Interventions

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (lenalidomide, dinutuximab, isotretinoin)

Lenalidomide DRUG

Given PO

Also known as: CC 5013, CC-5013, CC5013, CDC 501, Revlimid

Treatment (lenalidomide, dinutuximab, isotretinoin)

Pharmacological Study OTHER

Correlative studies

Treatment (lenalidomide, dinutuximab, isotretinoin)

Dinutuximab BIOLOGICAL

Given IV

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

Treatment (lenalidomide, dinutuximab, isotretinoin)

Isotretinoin DRUG

Given PO

Also known as: 13-cis retinoic acid, 13-cis-Retinoate, 13-cis-Retinoic Acid, 13-cis-Vitamin A Acid, 13-cRA, Absorica, Accure, Accutane, Amnesteem, cis-Retinoic Acid, Cistane, Claravis, Isotretinoinum, Isotrex, Isotrexin, Myorisan, Neovitamin A, Neovitamin A Acid, Oratane, Retinoicacid-13-cis, Ro 4-3780, Ro-4-3780, Roaccutan, Roaccutane, Roacutan, Sotret, ZENATANE

Treatment (lenalidomide, dinutuximab, isotretinoin)

Eligibility Criteria

• Age: Up to 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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
• Patients must have high-risk neuroblastoma
• Patients must have at least ONE of the following:
• Recurrent/progressive disease at any time prior to enrollment - regardless of response to frontline therapy
• Refractory disease: persistent sites of disease (after less than a partial response to frontline therapy, following a minimum of 4 cycles of induction therapy) AND patient has never had a relapse/progression
• Persistent disease: persistent disease after achieving at least a partial response to frontline therapy after a minimum of 4 cycles of induction therapy and patient has never had a relapse/progression
• Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below):
• Bone disease
• At least one metaiodobenzylguanidine (MIBG) avid bone site or diffuse MIBG uptake
• For recurrent/progressive or refractory disease a biopsy is not required regardless of number of MIBG avid lesions
• For persistent disease, if patient has only 1 or 2 MIBG avid lesions OR a Curie score of 1-2, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one site present at the time of enrollment (bone marrow, bone, or soft tissue) is required to be obtained at any time point prior to enrollment and two weeks subsequent to most recent prior therapy; if a patient has 3 or more MIBG avid lesions OR a Curie score of \>= 3 then no biopsy is required for eligibility
• If a tumor is known to be MIBG non-avid, then a patient must have at least one fludeoxyglucose (FDG)-positron emission tomography (PET) avid bone site present at the time of enrollment with biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma obtained at any time prior to enrollment and two weeks subsequent to most recent prior therapy
• Any amount of neuroblastoma tumor cells in the bone marrow based on routine morphology (with or without immunocytochemistry) in at least one sample from bilateral aspirates and biopsies
• At least one soft tissue lesion that meets the criteria for a TARGET lesion as defined by:
• SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter \>= 10 mm, or for lymph nodes \>= 15 mm on short axis; lesions meeting size criteria will be considered measurable

You may not qualify if:

• Quantitative serum b-HCG must be negative in girls who are post-menarchal; males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method; pregnant or breast-feeding women will not be entered on this study
• Breast feeding women are not eligible
• Patients who have an active or uncontrolled infection are excluded
• Patients with a paraben allergy cannot take isotretinoin preparations containing this compound (i.e. Accutane, Sotret) but are eligible if they can take an alternate preparation without paraben; (applicable only for entry onto dose levels receiving isotretinoin)
• Patients with a history of venous or arterial thrombosis personally before the age of 40 years unless associated with a central line
• Patients with a history of prior central nervous system (CNS) metastases or skull lesions with intracranial extension will be required to have a head computed tomography (CT) or magnetic resonance imaging (MRI) at study entry demonstrating no active CNS metastases; patients with skull metastases with associated intracranial soft tissue masses will remain eligible
• Inability to swallow lenalidomide capsules whole; capsules of 13-isotretinoin may be opened
• Patient declines participation in NANT 2004-05; unless the institution has been granted special exemption from mandatory enrollment on NANT 2004-05 by the NANT Operations Center

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (15)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, 94304, United States

Location

UCSF Medical Center-Parnassus

San Francisco, California, 94143, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

University of Chicago Comer Children's Hospital

Chicago, Illinois, 60637, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

dinutuximab; Isotretinoin; Lenalidomide

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)

Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Pigments, Biological; Biological Factors; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Araz Marachelian

  New Approaches to Neuroblastoma Treatment (NANT)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 18, 2012
• First Posted: October 22, 2012
• Study Start: February 4, 2013
• Primary Completion: September 14, 2018
• Study Completion (Estimated): March 3, 2027
• Last Updated: April 13, 2026

Record last verified: 2026-03

Locations

US (14); CA (1)