Ipilimumab With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Melanoma Mets Pts
The investigators want to study the safety, side effects, and benefits of TILs when they are given with the drug ipilimumab. Ipilimumab is a type of immunotherapy - a drug that is used to boost the ability of the immune system to fight cancer, infection, and other diseases.
Procedure: Tumor Infiltrating Lymphocytes (TIL)
Drug: Administration of Lymphodepletion
Drug: Cyclophosphamide as Part of Lymphodepletion
Drug: Fludarabine as Part of Lymphodepletion
Drug: High Dose IL-2
Biological: Adoptive Cell Therapy with TIL
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Co-stimulation With Ipilimumab to Enhance Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Patients With Metastatic Melanoma|
- Safety and Feasibility of Administering Ipilimumab with adoptive cell transfer (ACT) Using TIL [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]The data analysis will mainly be descriptive. All study results will be preliminary and of exploratory in nature due to the pilot status and small sample size of the trial. Feasibility is defined as the ability to deliver at least 50% (i.e., two out of four) of the planned doses of ipilimumab and successfully treat at least 60% (i.e., ≥6/10) of the patients with TIL. All patients will be evaluable for toxicity from the time of their first protocol treatment. Toxicity will be reported by type and severity according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) version 4.
- Overall Response Rate (ORR) [ Time Frame: 3 months ] [ Designated as safety issue: No ]Overall response (OR) is defined as the patient being alive at week 6, confirmed at week 12 and tumor size evaluated at both times using the Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria to be a complete response (CR) or partial response (PR). Evaluations will be made by computed tomography (CT) scan approximately 6 weeks after the cell infusion, then confirmed by CT scanning approximately 12 weeks after the cell infusion, and by clinical evaluation during the first 12 weeks. The overall response (CR+PR) rate will be summarized using both a point estimate and its exact confidence interval based on the binomial distribution.
- Progression Free Survival (PFS) [ Time Frame: 3 months ] [ Designated as safety issue: No ]Progression-free survival (PFS), defined as the time from study entry to disease progression, relapse or death due to any cause, whichever is earlier, will be summarized with the Kaplan-Meier curve. Confidence intervals for the median and survival rates at different time points will be constructed if needed and appropriate. This secondary endpoint will be reported descriptively.
|Study Start Date:||October 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Combination Therapy
The combination of ipilimumab followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2.
Pre-treatment with ipilimumab (cycle 1): Before the participant's tumor sample is taken to send to the lab for growing the TILs, they will start their first cycle of ipilimumab. This drug is given as an intravenous infusion (through a vein) over a period of about 90 minutes (an hour and a half). Cycle 2 of ipilimumab: About a week after the sample of the participant's tumor was collected for TIL growth (and 3 weeks after their first cycle of ipilimumab), participant's will have their second cycle of ipilimumab. This will be another IV infusion, lasting about 90 minutes.
Other Name: YervoyProcedure: Tumor Infiltrating Lymphocytes (TIL)
Tumor sample for TIL growth in the lab: About 2 weeks after the participant's first cycle of ipilimumab, a sample of their tumor will be collected and sent to the lab for TIL growth. Growing the TILs takes about 6 weeks. If their sample has grown enough TIL cells, participants will continue with the next part of the study. Depending on how long the TILs take to grow in the lab, they may need to repeat some of their laboratory and imaging tests (blood draws, X-rays, and CT or magnetic resonance imaging [MRI] scans). TIL Infusion (inpatient): After completing lymphodepletion, participants will be admitted back into the hospital for IV infusion of the TIL cells.Drug: Administration of Lymphodepletion
Lymphodepletion (inpatient hospital stay for about 2 days plus outpatient drug dosing for 5 days): About 4 weeks after their second cycle of ipilimumab, participants will be admitted to the hospital for their first two days of receiving the chemotherapy drug, cyclophosphamide. This drug will be given as an intravenous (IV, meaning through the vein) infusion. After 2 days of receiving cyclophosphamide, if their study doctor thinks that they are well enough, you will be discharged from the hospital and will return for the next 5 days in a row for outpatient IV infusions of the second lymphodepletion chemotherapy, fludarabine.Drug: Cyclophosphamide as Part of Lymphodepletion
Other Name: CytoxanDrug: Fludarabine as Part of Lymphodepletion
Other Name: FludaraDrug: High Dose IL-2
High dose IL-2 (continued inpatient): Participants will remain in the hospital following TIL infusion for receiving high dose IL-2 and recovery. The IL-2 will be given three times per day for about 3-5 days as an IV bolus (meaning through the vein, more quickly than other infusions - in about 15 minutes each dose). Participants will remain in the hospital for approximately 7-14 days until they have recovered from the IL-2 treatments.
Other Names:Biological: Adoptive Cell Therapy with TIL
Other Name: ACT
Please refer to this study by its ClinicalTrials.gov identifier: NCT01701674
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute||Recruiting|
|Tampa, Florida, United States, 33612|
|Contact: Erica Royster 813-745-4279 email@example.com|
|Principal Investigator: Amod Sarnaik, M.D.|
|Sub-Investigator: Heather Bridge, PA-C|
|Sub-Investigator: Geoffrey Gibney, M.D.|
|Sub-Investigator: William Janssen, Ph.D.|
|Sub-Investigator: Ragini Kudchadkar, M.D.|
|Sub-Investigator: Vernon Sondak, M.D.|
|Sub-Investigator: Melissa Thebeau, ARNP|
|Sub-Investigator: Jeffrey Weber, M.D., Ph.D.|
|Sub-Investigator: Jonathan Zager, M.D.|
|Sub-Investigator: Dima Abdul-Jabbar, M.D.|
|Sub-Investigator: Shilpa Gupta, M.D.|
|Sub-Investigator: Jinsong Zhang, M.D., Ph.D.|
|Principal Investigator:||Amod Sarnaik, M.D.||H. Lee Moffit Cancer Center and Research Institute|