Adoptive Cell Therapy Across Cancer Diagnoses
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|ClinicalTrials.gov Identifier: NCT03296137|
Recruitment Status : Recruiting
First Posted : September 28, 2017
Last Update Posted : August 1, 2018
|Condition or disease||Intervention/treatment||Phase|
|Cancer||Biological: Autologous tumor-infiltrating lymphocytes Drug: Ipilimumab Drug: Nivolumab Drug: proleukin Drug: Cyclophosphamide Drug: Fludara||Phase 1 Phase 2|
Adoptive cell therapy (ACT) is a personalized form of immunotherapy, where lymphocytes isolated from the patient's own tumor tissue are expanded 1000-fold ex-vivo and then infused back into the patient. The lymphocytes are then able to recognize and attack remaining cancer cells. This approach has shown remarkable clinical results in several trials conducted worldwide for patients with advanced melanoma - some with durable remissions. Promising clinical results were obtained in smaller trials where patients with disparate solid tumors were treated with tumor-infiltrating lymphocytes (TILs). At Center for Cancer Immune Therapy (CCIT) at Herlev Hospital, there are currently clinical trials undergoing in ovarian and renal cancer, and internationally ACT is being tested in an increasing number of cancer diagnoses, some trials are even recruiting patients across cancer types. Studies have shown that a high intratumoral infiltration with TILs in is correlated to the general clinical outcome of the disease in virtually all solid tumors, and thus clinical trials with TIL-based ACT to different cancer diagnoses have been undertaken.
To support the TIL-mediated tumor elimination, in classical ACT protocols patients go through a highly specialized treatment regime before and after TIL infusion. This regime includes lymphodepletion with 7 days non-myeloablative chemotherapy, to provide an immunological window of opportunity for the infused TILs, and concomitant immune stimulation with interleukin-2 (IL-2). Checkpoint inhibition to support the anti-tumor activity of TILs is currently under extensive investigation in several other trials worldwide. Thus, lymphodepletion and IL-2 stimulation are well-established as supportive therapy and already an integrated part of current ACT protocols and while checkpoint inhibition is a new addition at CCIT; internationally other centers have ongoing comparable trials.
Drug-based immunotherapy in the form of checkpoint inhibitors (anti-PD-1 and anti-CTLA-4) has yielded impressive clinical results across tumor histologies. Recent results indicate that the effect of immunotherapy relies not so much on the cancer diagnoses but rather on the genomic and immunologic features of the individual patient's cancer disease. Both ACT and checkpoint inhibition work by tipping the immunological balance in favor of activation and away from suppression or avoidance by the cancer cells. Scientific evidence now show that administering anti-CTLA-4 and PD-1 could provide a benefit in the ACT setting, and several ongoing clinical trials are testing combinations of ACT and checkpoint inhibition. To synergistically maximize the immunological potential, we wish to combine ACT with an anti-CTLA-4 antibody (Ipilimumab) prior to tumor resection and an anti-PD-1 antibody (Nivolumab) in combination with TIL infusion.
Patients will be treated with one dose of Ipilimumab 14 days before undergoing surgery to harvest tumor material for TIL production. Patients is admitted on day -8 in order to undergo lymphodepleting chemotherapy with cyclophosphamide and fludara starting day -7. On day -2 patients will start treatment with Nivolumab every 2 weeks for a total of 4 doses to increase the activity of the infused TIL product.
Available evidence indicates that ACT is a safe and feasible treatment option in an increasing number of solid tumors, and that it should be tested in all cancer patients regardless of their cancer diagnosis.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||25 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Adoptive Cell Therapy Across Cancer Diagnoses|
|Actual Study Start Date :||October 13, 2017|
|Estimated Primary Completion Date :||October 13, 2019|
|Estimated Study Completion Date :||March 13, 2020|
|Experimental: All participants||
Biological: Autologous tumor-infiltrating lymphocytes
Tumor-infiltrating lymphocytes grown ex-vivo from resected from cancer tissue and reapplied to the patient via an intravenous infusion.
One treatment with ipilimumab (3 mg/kg) prior to tumor resection.
4 doses of nivolumab. Starting 2 days prior to TIL infusion and every 2 weeks hereafter.
2 MIE s.c. injection, after TIL infusion and continuing for 2 weeks
2 doses (60 mg/kg) prior to TIL infusion
5 doses (25 mg/m2) prior to TIL infusion
- Number and type of reported adverse events [ Time Frame: Up to 2,5 years from begin of study ]Determine the safety of the administration of TIL therapy including checkpoint inhibitors, lymphodepleting chemotherapy and Interleukin-2 for patients with cancer by reporting adverse events according to CTCAE v. 4.0.
- Treatment response, progressive disease [ Time Frame: Up to 7 years from begin of study ]Clinical response in progression-free survival to treatment according to RECIST 1.1
- Treatment response, surival [ Time Frame: Up to 7 years from begin of study ]Clinical response in terms of overall survival.
- Treatment related immune response [ Time Frame: 3 years from begin of study ]Flow cytometry-based immunological evaluation of peripheral blood
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): NCT03296137
|Contact: Inge Marie Svane, MD, Profemail@example.com|
|Contact: Anders H Kverneland, MDfirstname.lastname@example.org|
|Center for Cancer immune Therapy (CCIT), Dept. of Hematology and dept. of Oncology||Recruiting|
|Copenhagen, Denmark, 2730|
|Contact: Anders H Kverneland, MD email@example.com|
|Principal Investigator:||Anders H Kverneland, MD||Center for Cancer Immune Therapy, Herlev Hospital|
|Study Director:||Inge Marie Svane, MD, Prof.||Center for Cancer Immune Therapy, Herlev Hospital|