NCT01711554

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

A Phase I Study of Lenalidomide and Anti-GD2 Mab Ch14.18 +/- Isotretinoin in Patients With Refractory/Recurrent Neuroblastoma

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

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.

Detailed description

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D) of lenalidomide in combination with fixed doses of dinutuximab (ch14.18) and isotretinoin given to children with refractory or recurrent neuroblastoma. II. To define the toxicities of lenalidomide administered in combination with ch14.18 and isotretinoin. III. To describe the differences in immune function modulation between "low" versus "high" dose lenalidomide given with ch14.18 and isotretinoin. SECONDARY OBJECTIVES: I. To determine the pharmacokinetics of lenalidomide given in this combination regimen. II. To determine the steady state pharmacokinetics of isotretinoin (day 28, course one) given in combination with lenalidomide. III. To measure peak and trough levels of ch14.18 in patients receiving lenalidomide and to compare to historical controls of patients receiving ch14.18 in combination with interleukin 2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF). IV. To describe the immunological effects of lenalidomide (T cells, natural killer \[NK\] cells, monocytes, cytokines, chemokines) within this three drug regimen. V. To define the incidence and titers of human anti-chimeric antibody (HACA) on this regimen. VI. To describe, within the context of a phase I study, the response rate to lenalidomide combined with ch14.18 and isotretinoin in patients with recurrent/refractory neuroblastoma. VII. To summarize, within the context of a phase I study, the event-free survival of patients with recurrent/refractory neuroblastoma or in complete response (CR) after progressing, and who are treated with lenalidomide combined with ch14.18 and isotretinoin. VIII. To determine, within the context of a phase I study, if killer-cell immunoglobulin-like receptor (KIR) receptor-ligand mismatch or specific Fc gamma receptor (Fc gamma R) alleles are associated with anti-tumor response. IX. To quantify neuroblastoma tumor cell "load" using a 5-gene TaqMan Low Density Array (TLDA) assay in peripheral blood at study entry, following, with each disease evaluation and at end of therapy and bone marrow at study entry, with each response evaluation when bone marrow is sampled, and at end of therapy. X. To compare the toxicities of this regimen with the historical toxicity data from the Children's Oncology Group (COG) ANBL0032 and ANBL0931 studies of ch14.18 with IL-2, GM-CSF and isotretinoin. XI. To describe the tolerability and ability to give full doses of ch14.18 and lenalidomide over extended periods of time, i.e. in courses 6-12. OUTLINE: This is a dose-escalation study of lenalidomide. Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21, dinutuximab intravenously (IV) over 10 hours on days 8-11, and isotretinoin PO twice daily (BID) on days 15-28. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up periodically.

Conditions

• Recurrent Neuroblastoma
• Refractory Neuroblastoma

Interventions

Type	Name	Description
BIOLOGICAL	Dinutuximab	Given IV
DRUG	Isotretinoin	Given PO
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Lenalidomide	Given PO
OTHER	Pharmacological Study	Correlative studies

Timeline

• Start date: 2013-02-04
• Primary completion: 2018-09-14
• Completion: 2027-03-03
• First posted: 2012-10-22
• Last updated: 2026-04-13

Locations

15 sites across 2 countries: United States, Canada