Humanized 3F8 Monoclonal Antibody (Hu3F8) When Combined With Interleukin-2 in Patients With High-Risk Neuroblastoma and GD2-positive Solid Tumors
The purpose of this study is to find out if "humanized 3F8" (Hu3F8) when combined with interleukin-2 (rIL2) is safe for treating neuroblastoma and other cancers. A phase 1 study means the investigators are trying to find out what side effects happen when higher and higher doses of a drug are used.
The investigators want to find out what effects, good and/or bad, Hu3F8 combined with rIL2 has on cancer. The amount of Hu3F8 that patients gets will depend on when they start treatment on this study. The amount of rIL2 will be the same for all patients. The investigators also want to find out more about how Hu3F8 works and how effective it is in attacking the disease when combined with rIL2.
|Neuroblastoma||Drug: 3F8 Monoclonal Antibody Combined with Interleukin-2||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I Study of Humanized 3F8 Monoclonal Antibody (Hu3F8) When Combined With Interleukin-2 in Patients With High-Risk Neuroblastoma and GD2-positive Solid Tumors|
- maximum tolerated dosage [ Time Frame: 1 year ]of hu3F8 when combined with rIL-2. six dosage levels of hu3F8 will be tested with three to six patients at each dosage level.
- pharmacokinetics [ Time Frame: 1 year ]of iv hu3F8 in the presence of rIL-2. Pharmacokinetics will be measured by serial blood sampling following the first two iv doses of hu3F8. Serum hu3F8 will be measured at time 0, 5 min, 3h, 6-8h, 24h, 48h, 72h, 96, 120h and 168h after infusion for each of the two hu3F8 injections during the first cycle. Peak hu3F8 level at 5 min after infusion will also be measured for all hu3F8 infusions during all other cycles. PK analysis will be carried out by noncompartmental analysis of the serum concentration-time data using the WinNonlin software program (Pharsight Corp., Mountain View, CA).
- anti-tumor activity [ Time Frame: 1 year ]of hu3F8 plus rIL-2 against NB and other GD2-positive tumors. For neuroblastoma, anti-tumor activity will be measured by international neuroblastoma response criteria (INRC).90 For other solid tumors, the response and progression will be evaluated in this study using the Response Evaluation Criteria in Solid Tumors (RECIST) Committee, version 1.1.
- biologic correlates with hu3F8 dose [ Time Frame: 1 year ]Biologic correlate studies include (1) host immunity and (2) host WBC cytolytic capacity. The parameters measured for each patient under "host immunity" include: the induction of HAMA or HAHA, the induction of Ab3, the induction of Ab3', the induction of antibody response to tumor antigen and secondary cytokine profile.
- quantification of pain [ Time Frame: 1 year ]As patient's pain will be assessed with a numerical score of 1 to 10 over the course of the treatment, a curve of pain intensity over time can be generated for each patient. We have been collecting similar pain data for patients being treated with murine 3F8 (control group) and Hu3F8 alone and may be able use this to compare to pain data of patients receiving hu3F8 and rIL2. Because the first dose of hu3F8 will be given without rIL2 and the second dose with rIL2, we will also be able to directly compare the pain associated with hu3F8 with and without rIL2 in the same patient. This pain level will be compared to the pain scores in patients receiving m3F8 on concurrent protocols at 80 mg/m2/day or 20 mg/m2/day. Differences will be tested for significance using both Mann-Whitney and repeated measures ANOVA tests as described previously.
|Study Start Date:||August 2012|
|Estimated Study Completion Date:||August 2018|
|Estimated Primary Completion Date:||August 2018 (Final data collection date for primary outcome measure)|
Experimental: hu3F8 and rIL-2
This phase I single arm trial assesses the toxicity of escalating doses of hu3F8 (day 1 and day 8) in the presence of 6 × 10^6 U rIL-2/m^2/d x 5 days sc (day 8 through day 12). These 2 doses of hu3F8 and 5 doses of rIL-2 constitute a treatment cycle.
Drug: 3F8 Monoclonal Antibody Combined with Interleukin-2
One cycle has 2 days of intravenous hu3F8 treatment, given about 7 days apart. rIL-2 is administered sc daily over 5 days, beginning on the second infusion of hu3F8. To limit side-effects, patients receive analgesics and antihistamines as premedications. Cycles are 21 days. Patients can have up to 4 cycles of treatment on this study within 18 months of starting hu3F8.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01662804
|United States, New York|
|Memorial Sloan Kettering Cancer Center|
|New York, New York, United States, 10065|
|Principal Investigator:||Stephen Roberts, MD||Memorial Sloan Kettering Cancer Center|