CancerPhase 1/2NCT03296137
Adoptive Cell Therapy Across Cancer Diagnoses
A Phase 1/2 study testing Autologous tumor-infiltrating lymphocytes, Ipilimumab and Nivolumab in people with Cancer, run by Inge Marie Svane at 1 site in Denmark.
Trial summary
This study will perform tumor-infiltrating lymphocyte (TIL)-based adoptive T-cell therapy in combination with checkpoint inhibition on cancer patients across all cancer diagnoses. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Cancer
- What is being tested?
- Autologous tumor-infiltrating lymphocytes, Ipilimumab and Nivolumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteDenmark
- Study dates
- 13 Oct 2017to 1 Jul 2020
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically verified metastatic or locally advanced cancer diagnosis
- At least one lesion (>1 cm3) available for surgical resection
- Not candidate for standard treatment options
- Age of 18-70 years
- Performance status of 1 or 0.
- Life expectancy > 6 months
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- One or more measurable parameter according to RECIST 1.1.
- No significant toxicity from previous cancer treatments (CTC≤1). Except alopecia (CTC≤2) or neuropathy (CTC≤2)
- Sufficient organ function, including:
- Absolute neutrophil count (ANC) ≥ 1.500 /µl
- Leucocyte count ≥ normal limit
- Platelets ≥ 100.000 /µl and <700.000 /µl
- Hemoglobin ≥ 6,0 mmol/l (regardless of prior transfusion)
- S-creatinine < 140
- S-bilirubin ≤ 1,5 times upper normal limit
- ASAT/ALAT ≤ 2,5 times upper normal limit
- Alkaline phosphatase ≤ 5 times upper normal limit
- Lactate dehydrogenase (LDH) ≤ 5 times upper normal limit
- Sufficient coagulation: PP-time>40 and INR<1,5
- Women in the fertile age must use effective contraception. This applies from inclusion and until 6 months after treatment. Birth control pills, spiral, depot injection with gestagen, subdermal implantation, hormonal vaginal ring and transdermal depot patch are all considered safe contraceptives.
- Signed statement of consent after receiving oral and written study information
- Willingness to participate in the planned treatment and follow-up and capable of handling toxicities.
Who cannot join
- A history of prior malignancies. Patients treated for another malignancy can only participate if they are without signs of disease for a minimum of 3 years after last treatment.
- Primary brain tumor or verified brain metastases
- Known hypersensitivity to one of the active drugs or excipients.
- Significant medical conditions, including but not limited to severe asthma/COLD, significant cardiac disease, poorly regulated insulin dependent diabetes mellitus.
- Creatinine clearance below 70 ml/min .
- Acute or chronic infections with HIV, hepatitis, syphilis etc.
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- Severe allergies or previous anaphylactic reactions.
- Active autoimmune disease, such as autoimmune neutropenia/thrombocytopenia or hemolytic anemia, systemic lupus erythematosus, Sjögren's syndrome, sclerodermia, myasthenia gravis, goodpastures disease, addison's disease, hashimoto's thyroiditis, graves' disease etc.
- Pregnant women and women who are breastfeeding.
- Simultaneous treatment with systemic immunosuppressive drugs (including prednisolone methotrexate etc.)
- Simultaneous treatment with other experimental drugs.
- Simultaneous treatment with other systemic anti-cancer treatments.
- Patients with active or uncontrollable hypercalcemia.
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Cancer immune Therapy (CCIT), Dept. of Hematology and dept. of Oncology
Copenhagen, 2730
About this study
This study will perform tumor-infiltrating lymphocyte (TIL)-based adoptive T-cell therapy in combination with checkpoint inhibition on cancer patients across all cancer diagnoses.
Read the detailed description
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.
- Conditions
- Cancer
- Being tested
- Autologous tumor-infiltrating lymphocytes, Ipilimumab, Nivolumab, proleukin, Cyclophosphamide
- Keywords
- immune therapy, TILs, Adoptive cell therapy
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Autologous tumor-infiltrating lymphocytesBiological
Tumor-infiltrating lymphocytes grown ex-vivo from resected from cancer tissue and reapplied to the patient via an intravenous infusion.
IpilimumabDrug
One treatment with ipilimumab (3 mg/kg) prior to tumor resection.
NivolumabDrug
4 doses of nivolumab. Starting 2 days prior to TIL infusion and every 2 weeks hereafter.
proleukinDrug
2 MIE s.c. injection, after TIL infusion and continuing for 2 weeks
CyclophosphamideDrug
2 doses (60 mg/kg) prior to TIL infusion
FludaraDrug
5 doses (25 mg/m2) prior to TIL infusion
| Study group | Role | What they receive |
|---|---|---|
| Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors | Experimental | Not described Receives: Biological: Autologous tumor-infiltrating lymphocytes; Drug: Ipilimumab; Drug: Nivolumab; Drug: proleukin; Drug: Cyclophosphamide; Drug: Fludara |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants and Type of Reported Adverse Events
Determine the safety of the administration of TIL therapy including checkpoint inhibitors, lymphodepleting chemotherapy and Interleukin-2 for patients with cancer by reporting grade >2 adverse events according to CTCAE v. 4.0
Measured: Up to 2,5 years from begin of study
Secondary outcomes (3)
Time to Disease Progression
Days of follow-up from TIL infusion until progressive cancer disease, end of follow-up or death.
Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions
Measured: Until study completion
Overall Survival
Duration of survival measured in days after adoptive cell therapy until death or end of follow-up/censoring.
Measured: Until study completion
Overall Response Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by CAT scan: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR.
Measured: The patients were evaluated every 6-12 weeks (median 90 days) and after therapy and until study completion (max 220 days).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2017
- Study start13 Oct 2017
- Primary completion13 Mar 2020
- Study completion1 Jul 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Inge Marie Svane
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Inge Marie Svane, Herlev Hospital
- Investigators
- Anders H Kverneland, MD, Principal investigator, Center for Cancer Immune Therapy, Herlev HospitalInge Marie Svane, MD, Prof., Study director, Center for Cancer Immune Therapy, Herlev Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03296137
- Sponsor's protocol ID
- AA1720
- Status last verified
- Oct 2024
- First submitted
- 18 Sep 2017
- Last updated
- 26 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Kverneland AH, Chamberlain CA, Borch TH, Nielsen M, Mork SK, Kjeldsen JW, Lorentzen CL, Jorgensen LP, Riis LB, Yde CW, Met O, Donia M, Svane IM. Adoptive cell therapy with tumor-infiltrating lymphocytes supported by checkpoint inhibition across multiple solid cancer types. J Immunother Cancer. 2021 Oct;9(10):e003499. doi: 10.1136/jitc-2021-003499.
PubMed 34607899
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Cell Therapy Across Cancer Diagnoses
- ClinicalTrials.gov ID
- NCT03296137
- Acronym / sponsor ID
- AA1720
- Conditions
- Cancer
- Keywords
- immune therapy, TILs, Adoptive cell therapy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Inge Marie SvaneUniversity, hospital or other
- Study start
- 13 Oct 2017 (actual)
- Primary completion
- 13 Mar 2020 (actual)
- Study completion
- 1 Jul 2020 (actual)
- First posted
- 28 Sep 2017 (actual)
- Results
- Posted 26 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will perform tumor-infiltrating lymphocyte (TIL)-based adoptive T-cell therapy in combination with checkpoint inhibition on cancer patients across all cancer diagnoses.
Detailed description
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors | Experimental | Biological: Autologous tumor-infiltrating lymphocytes, Drug: Ipilimumab, Drug: Nivolumab, Drug: proleukin, Drug: Cyclophosphamide, Drug: Fludara |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Histologically verified metastatic or locally advanced cancer diagnosis
- At least one lesion (>1 cm3) available for surgical resection
- Not candidate for standard treatment options
- Age of 18-70 years
- Performance status of 1 or 0.
Key exclusion criteria (13 listed)
- A history of prior malignancies. Patients treated for another malignancy can only participate if they are without signs of disease for a minimum of 3 years after last treatment.
- Primary brain tumor or verified brain metastases
- Known hypersensitivity to one of the active drugs or excipients.
- Significant medical conditions, including but not limited to severe asthma/COLD, significant cardiac disease, poorly regulated insulin dependent diabetes mellitus.
- Creatinine clearance below 70 ml/min .
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Autologous tumor-infiltrating lymphocytesTumor-infiltrating lymphocytes grown ex-vivo from resected from cancer tissue and reapplied to the patient via an intravenous infusion. | Biological | Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors |
| IpilimumabOne treatment with ipilimumab (3 mg/kg) prior to tumor resection. | Drug | Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors |
| Nivolumab4 doses of nivolumab. Starting 2 days prior to TIL infusion and every 2 weeks hereafter. | Drug | Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors |
| proleukin2 MIE s.c. injection, after TIL infusion and continuing for 2 weeks | Drug | Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors |
| Cyclophosphamide2 doses (60 mg/kg) prior to TIL infusion | Drug | Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors |
| Fludara5 doses (25 mg/m2) prior to TIL infusion | Drug | Tumor-infiltrating Lymphocyte (TIL) Therapy with checkpoint inhibitors |
Primary outcome
Number of Participants 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 grade >2 adverse events according to CTCAE v. 4.0
3 secondary outcomes
Time to Disease Progression
Time frame: Until study completion
Overall Survival
Time frame: Until study completion
Overall Response Rate
Time frame: The patients were evaluated every 6-12 weeks (median 90 days) and after therapy and until study completion (max 220 days).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34607899Kverneland AH, Chamberlain CA, Borch TH, Nielsen M, Mork SK, Kjeldsen JW, Lorentzen CL, Jorgensen LP, Riis LB, Yde CW, Met O, Donia M, Svane IM. Adoptive cell therapy with tumor-infiltrating lymphocytes supported by checkpoint inhibition across multiple solid cancer types. J Immunother Cancer. 2021 Oct;9(10):e003499. doi: 10.1136/jitc-2021-003499.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anders H Kverneland, MD principal investigator
Center for Cancer Immune Therapy, Herlev Hospital
Inge Marie Svane, MD, Prof. study director
Center for Cancer Immune Therapy, Herlev Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Autologous tumor-infiltrating lymphocytes, Ipilimumab and Nivolumab in people with Cancer, run by Inge Marie Svane at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 22 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants and Type of Reported Adverse Events (time frame: Up to 2,5 years from begin of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03296137, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2024.