Lorvotuzumab Mertansine in Treating Younger Patients With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor, or Synovial Sarcoma
Recurrent Malignant Peripheral Nerve Sheath Tumor
Recurrent Synovial Sarcoma
Other: Laboratory Biomarker Analysis
Biological: Lorvotuzumab Mertansine
Other: Pharmacological Study
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Study of IMGN901 (Lorvotuzumab Mertansine; IND #: TBD, NSC: 783609) in Children With Relapsed or Refractory Wilms Tumor, Rhabdomyosarcoma, Neuroblastoma, Pleuropulmonary Blastoma, Malignant Peripheral Nerve Sheath Tumor (MPNST) and Synovial Sarcoma|
- Incidence of toxicities of lorvotuzumab mertansine, using the NCI Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 12 months (17 courses) ] [ Designated as safety issue: Yes ]Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. Toxicity information recorded will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen.
- Objective response by Response Evaluation Criteria in Solid Tumors version 1.1 [ Time Frame: Up to 18 weeks (6 courses) ] [ Designated as safety issue: No ]The best response of disease will be examined separately in each stratum. A responder is defined as a patient who achieves a best response of partial response or complete response on the study. Response rates will be calculated as the percent of evaluable patients who are responders, and confidence intervals will be constructed accounting for the two-stage design.
- CD56 expression [ Time Frame: Day 1 and 8 of course 1 prior to lorvotuzumab mertansine ] [ Designated as safety issue: No ]The association between CD56+ expression and response will be evaluated using the exact conditional test of proportions (Fisher's Exact test). Analyses will be descriptive and exploratory and hypotheses generating in nature.
- Pharmacokinetic (PK) parameters of lorvotuzumab mertansine [ Time Frame: Pre-treatment, end of infusion, and 2, 6, 24, 48, and 96 hours after end of infusion on day 1 of course 1, and pre-treatment, end of infusion, and 2 and 6 hours after end of infusion on day 8 of course 1 ] [ Designated as safety issue: No ]A descriptive analysis of PK parameters of lorvotuzumab mertansine will be performed to define systemic exposure, drug clearance, and other pharmacokinetic parameters. The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit). Analyses will be descriptive and exploratory and hypotheses generating in nature.
|Study Start Date:||May 2015|
|Estimated Primary Completion Date:||March 2019 (Final data collection date for primary outcome measure)|
Experimental: Treatment (lorvotuzumab mertansine)
Patients receive lorvotuzumab mertansine IV over 1 hour on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
Other: Laboratory Biomarker Analysis
Correlative studiesBiological: Lorvotuzumab Mertansine
Other Names:Other: Pharmacological Study
I. To assess the efficacy of IMGN901 (lorvotuzumab mertansine) in Wilms tumor, rhabdomyosarcoma and neuroblastoma and other cluster of differentiation (CD)56-expresing tumors such as pleuropulmonary blastoma, malignant peripheral nerve sheath tumor (MPNST) and synovial sarcoma.
II. To determine the tolerability of the adult recommended phase 2 dose (RP2D) of IMGN901 administered as an intravenous infusion, administered on days 1 and 8 of a 21-day cycle, to children with refractory Wilms tumor, rhabdomyosarcoma, neuroblastoma, pleuropulmonary blastoma, MPNST, or synovial sarcoma.
III. To define and describe the toxicities of IMGN901 administered on this schedule.
I. To correlate tumor response with tumor CD56+ expression. II. To characterize the pharmacokinetics of IMGN901 in children with refractory cancer, including an assessment of impact on circulating CD56+ peripheral blood cells.
Patients receive lorvotuzumab mertansine intravenously (IV) over 1 hour on days 1 and 8. Treatment repeats every 21 days for up to 17 courses in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 5 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02452554
|United States, Pennsylvania|
|Children's Oncology Group||Not yet recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: James I. Geller, MD 513-636-6312 James.Geller@cchmc.org|
|Principal Investigator: James I. Geller, MD|
|Principal Investigator:||James Geller, MD||Children's Oncology Group|