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

Status
Active
Cancer Type
Neuroblastoma
Trial Phase
Phase I
Eligibility
21 and under, Male and Female
Study Type
Biomarker/Laboratory analysis
Treatment
NCD ID
NCT01711554
Protocol IDs
NCI-2012-02011 (primary)
NANT N2011-04
P01CA081403
Study Sponsor
National Cancer Institute

Summary

This phase I trial studies the side effects and best dose of lenalidomide when given together with monoclonal antibody with or without isotretinoin in treating younger patients with refractory or recurrent neuroblastoma. Drugs used in chemotherapy, such as lenalidomide and isotretinoin, work in different wants to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as monoclonal antibody Ch14.18, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Giving more than one drug (combination chemotherapy) together with monoclonal antibody therapy may kill more tumor cells

Objectives

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 ch14.18 (monoclonal antibody Ch14.18) given intravenously (IV) for four days (days 8-11) and isotretinoin given twice each day orally for 14 days (days 15-28) and repeated every 28 days 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 sargramostim (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 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.

IX. 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.

OUTLINE: This is a dose-escalation study of lenalidomide.

Patients receive lenalidomide orally (PO) once daily (QD) on days 1-21, monoclonal antibody Ch14.18 IV over 10 hours on days 8-11, and isotretinoin PO twice daily (BID) on days 15-28 of dose levels 2-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up periodically.

Treatment Sites in Georgia


Aflac Cancer and Blood Disorders Center of Children’s at Egleston
1405 Clifton Road NE
3rd Floor
Atlanta, GA 30322
404-785-0853
www.choa.org