A Phase I Study of Lenalidomide and Anti-GD2 Mab Ch14.18 +/- Isotretinoin in Patients With Refractory/Recurrent Neuroblastoma.
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
II. To define the toxicities of lenalidomide administered in combination with ch14.18 and
III. To describe the differences in immune function modulation between "low" versus "high"
dose lenalidomide given with ch14.18 and isotretinoin.
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
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
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.
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
MTD defined as the highest dose level tested at which 0/6 or 1/6 patients experience dose-limiting toxicity (DLT) graded using the 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 theses toxicities and side effects by dose level and by course.
New Approaches to Neuroblastoma Therapy Consortium
United States: Food and Drug Administration
|Children's Hospital of Philadelphia||Philadelphia, Pennsylvania 19104|
|Dana-Farber Cancer Institute||Boston, Massachusetts 02115|
|Children's Hospital Los Angeles||Los Angeles, California 90027-0700|
|Cincinnati Children's Hospital Medical Center||Cincinnati, Ohio 45229-3039|
|Duke University Medical Center||Durham, North Carolina 27710|
|Texas Children's Hospital||Houston, Texas|
|University of Chicago Comprehensive Cancer Center||Chicago, Illinois 60637-1470|
|Seattle Children's Hospital||Seattle, Washington 98105|
|Cook Children's Medical Center||Fort Worth, Texas 76104|
|C S Mott Children's Hospital||Ann Arbor, Michigan 48109|
|Children's Healthcare of Atlanta - Egleston||Atlanta, Georgia 30322|
|Lucile Packard Children's Hospital Stanford University||Palo Alto, California 94304|
|University of California San Francisco Medical Center-Parnassus||San Francisco, California 94143|