Lenalidomide and Dinutuximab With or Without Isotretinoin in Treating Younger Patients With Refractory or Recurrent Neuroblastoma
|ClinicalTrials.gov Identifier: NCT01711554|
Recruitment Status : Suspended (Scheduled interim monitoring)
First Posted : October 22, 2012
Last Update Posted : October 25, 2018
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Neuroblastoma Refractory Neuroblastoma||Biological: Dinutuximab Drug: Isotretinoin Other: Laboratory Biomarker Analysis Drug: Lenalidomide Other: Pharmacological Study||Phase 1|
Show Detailed Description
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||62 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Study of Lenalidomide and Anti-GD2 Mab Ch14.18 +/- Isotretinoin in Patients With Refractory/Recurrent Neuroblastoma|
|Actual Study Start Date :||February 4, 2013|
|Estimated Primary Completion Date :||December 31, 2018|
Experimental: Treatment (lenalidomide, dinutuximab, isotretinoin)
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.
Other: Laboratory Biomarker Analysis
Other: Pharmacological Study
- 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 [ Time Frame: Up to 28 days ]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.
- Recommended phase II dose [ Time Frame: Up to 28 days ]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.
- Overall survival [ Time Frame: 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 ]Will be summarized with Kaplan-Meier plots.
- Event-free survival [ Time Frame: 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 ]Will be summarized with Kaplan-Meier plots.
- Changes in the levels of T cells, natural killer (NK) cells, monocytes, cytokines, and chemokines [ Time Frame: Baseline to up to 28 days ]These levels and the changes relative to baseline will be summarized by dose level by simple summary statistics: means (possibly after transformation) or medians, ranges, and standard deviations (if numbers and distribution permit). Scatterplots will be used to explore possible associations between the dose and day and toxicity experienced (as reflected in the maximum grade of toxicity experienced, infections or platelet recovery).
- Changes in levels of HACA (or other genotype) and tumor response [ Time Frame: Baseline to up to 3 years ]These levels and the changes relative to baseline will be summarized by dose level by simple summary statistics: means (possibly after transformation) or medians, ranges, and standard deviations (if numbers and distribution permit). Scatterplots will be used to explore possible associations between the dose and day and toxicity experienced (as reflected in the maximum grade of toxicity experienced, infections or platelet recovery).
- Pharmacokinetic determinations of lenalidomide [ Time Frame: Baseline, at 60 and 90 minutes, at 2, 6, 24 hours and days 7 and 22 after last dose of lenalidomide in course 1 ]These will be summarized by dose level with simple summary statistics: means (possibly after transformation) or medians, ranges, and standard deviations (if numbers and distribution permit). Scatterplots will be used to explore possible associations between the dose and estimates of the pharmacokinetic parameters, and between the pharmacokinetic determinations and toxicity experienced (as reflected in the maximum grade of toxicity experienced or in clinical measurements).
- Changes in TaqMan low density array (TLDA) scores [ Time Frame: Baseline to up to 3 years ]Standard descriptive summaries as well as scatterplots will be used. The association between the changes in TLDA scores and overall tumor response will also be summarized graphically and quantitatively. Changes (from baseline) in the TLDA scores over the course of treatment will be plotted and summarized by dose level and course.
- Overall response [ Time Frame: Up to 3 years ]The association between the changes in TLDA scores and overall tumor response will be summarized graphically and quantitatively.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01711554
|United States, California|
|Children's Hospital Los Angeles|
|Los Angeles, California, United States, 90027|
|Lucile Packard Children's Hospital Stanford University|
|Palo Alto, California, United States, 94304|
|UCSF Medical Center-Parnassus|
|San Francisco, California, United States, 94143|
|United States, Colorado|
|Children's Hospital Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Georgia|
|Children's Healthcare of Atlanta - Egleston|
|Atlanta, Georgia, United States, 30322|
|United States, Illinois|
|University of Chicago Comer Children's Hospital|
|Chicago, Illinois, United States, 60637|
|United States, Massachusetts|
|Boston Children's Hospital|
|Boston, Massachusetts, United States, 02115|
|United States, Michigan|
|C S Mott Children's Hospital|
|Ann Arbor, Michigan, United States, 48109|
|United States, North Carolina|
|UNC Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Texas|
|Cook Children's Medical Center|
|Fort Worth, Texas, United States, 76104|
|United States, Washington|
|Seattle Children's Hospital|
|Seattle, Washington, United States, 98105|
|Hospital for Sick Children|
|Toronto, Ontario, Canada, M5G 1X8|
|Principal Investigator:||Araz Marachelian||New Approaches to Neuroblastoma Treatment (NANT)|