Nivolumab and Tumor Infiltrating Lymphocytes (TIL) in Advanced Non-Small Cell Lung Cancer
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|ClinicalTrials.gov Identifier: NCT03215810|
Recruitment Status : Active, not recruiting
First Posted : July 12, 2017
Last Update Posted : May 12, 2020
|Condition or disease||Intervention/treatment||Phase|
|Non-Small Cell Lung Cancer Metastatic Non-small Cell Lung Cancer Squamous Cell Carcinoma Advanced NSCLC Adenosquamous Carcinoma Adenocarcinomas||Procedure: Tumor-infiltrating Lymphocytes (TIL) Drug: Nivolumab Drug: Cyclophosphamide Drug: Fludarabine Other: Tumor-infiltrating Lymphocyte Therapy Drug: Interleukin-2 (IL2)||Phase 1|
In this study, these special immune T-cells will be taken from a sample of the participant's tumor tissue that will be surgically removed. Certain parts of these cells will be multiplied, or grown, in the laboratory, using the drug interleukin-2 (IL-2) during part of the process. They will then be given back to the participant by an infusion in their veins. These cells are called tumor- infiltrating lymphocytes (TILs). The use of TILs involves a combination of drugs, including the following:
- Fludarabine and cyclophosphamide - two types of chemotherapy drugs. These drugs will be used for what is called lymphodepletion. The purpose of lymphodepletion in this study is to temporarily reduce the number of normal lymphocytes circulating in the participant's body before they are given the TILs that were grown in the lab. This is so that there will be more "space" for the lymphocytes (TILs) that will be infused in their veins.
- Interleukin-2 (IL-2) - a drug used to help the body's response to treatment on the immune system. A high dose regimen of IL-2 will be given after the participant receives the infusion of the T-cells.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase I Clinical Trial Combining Nivolumab and Tumor Infiltrating Lymphocytes (TIL) for Patients With Advanced Non-Small Cell Lung Cancer|
|Actual Study Start Date :||October 11, 2017|
|Estimated Primary Completion Date :||December 2020|
|Estimated Study Completion Date :||December 2021|
Experimental: TIL+ Nivolumab
Tumor-infiltrating Lymphocyte Therapy (TIL) + Nivolumab Treatment Plan: Tumor harvest, Tumor-infiltrating Lymphocytes growth, 4 cycles of nivolumab, cytoreductive chemotherapy with cyclophosphamide and fludarabine, TIL infusion, Interleukin-2 treatment.
Procedure: Tumor-infiltrating Lymphocytes (TIL)
Tumor harvest for TIL growth in the lab: A sample of the participant's tumor will be collected and sent to the lab for TIL growth. TIL will be prepared and cryopreserved.
Other Name: TIL
Nivolumab will be administered intravenously at a fixed dose of 240 mg for 4 doses every 2 weeks prior to TIL. Nivolumab dose will be fixed at 480 mg every 4 weeks up to 12 months after TIL.
Other Name: Opdivo
Cyclophosphamide will be administered at 60 mg/kg/day IV in 250 mL normal saline (NS) over approximately 2 hours. Cyclophosphamide will be initiated seven days prior to the anticipated TIL transfer, and the precise timing will depend on the rate of in vitro TIL growth. The dose will be based on the patient's body weight, but to prevent undue toxicity, it will not exceed a dose greater than 140% of the maximum ideal body weight per Metropolitan Life Insurance Company, Height and Weight Table.
Other Name: Cytoxan
After administration of Cyclophosphamide, Fludarabine will then be infused at 25 mg/m^2 intravenous piggyback (IVPB) daily over approximately 30 minutes starting 5 days prior to TIL transfer. To prevent undue toxicity with fludarabine, the dose will be based on body surface area (BSA), but will not exceed a dose calculated on surface areas based on body weights greater than 140% of the maximum ideal body weight per Metropolitan Life Insurance Company Height and Weight Tables.
Other Name: Fludara
Other: Tumor-infiltrating Lymphocyte Therapy
On day 0, all patients will receive TIL administered according to the current Moffitt Cell Therapy TIL Standard Operating Procedure (SOP). Eight (8) to twelve (12) hours after completing the TIL infusion, all participants will begin intermediate-dose decrescendo interleukin-2 (IL-2).
Other Name: TIL
Drug: Interleukin-2 (IL2)
Interleukin-2 (IL-2) - a drug used to help the body's response to treatment on the immune system. A high dose regimen of IL-2 will be given after the infusion of the T-cells.
- Rate of Dose Limiting Toxicity (DLT) [ Time Frame: Up to 40 months ]Investigators plan to demonstrate that treatment with nivolumab in patients undergoing TIL therapy is safe with a continuous Pocock-type stopping boundary for serious toxicity of < 17%, with safety reported based upon Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 criteria. DLT defined as: any grade ≥3 immune-related adverse event definitely attributable to nivolumab. DLT related to adoptive cell therapy will be defined as a non-hematologic grade 4 or higher adverse event that is immediately life-threatening occurring upon or after the start of therapy that is immediately life-threatening and not related to non-small cell lung cancer or other pre-existing condition. Safety: Toxicity will be assessed within 4 weeks of the adoptive TIL transfer. The accrual will be halted if excessive numbers of participants with toxicity are seen. For example, if there are 5 or more out of 10 participants (full follow-up) with toxicity, the trial will be stopped.
- Objective Response Rate (ORR) [ Time Frame: Up to 40 months ]Objective response rate associated with the treatment regimen. The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment will depend on the achievement of both measurement and confirmation criteria. Investigators plan to see if the treatment produces a best overall radiologic response rate in patients who progress on nivolumab monotherapy in unselected NSCLC of 20% or more. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD) taking as references the smallest sum LD.
- Progression Free Survival (PFS) [ Time Frame: Up to 40 months ]Progression free survival associated with the treatment regimen. 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. Progression (PD): At least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03215810
|United States, Florida|
|University of Florida Health Cancer Center.|
|Gainesville, Florida, United States, 32608|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Ben Creelan, M.D.||H. Lee Moffitt Cancer Center and Research Institute|