Metastatic MelanomaPhase 1/2NCT02379195
Peginterferon and TIL Therapy for Metastatic Melanoma
A Phase 1/2 study testing Cyclophosphamide, Fludarabine and TIL infusion in people with Metastatic Melanoma, run by Inge Marie Svane at 1 site in Denmark.
Trial summary
Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from the patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- Cyclophosphamide, Fludarabine and TIL infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteDenmark
- Study dates
- Nov 2014to Oct 2018
- 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 confirmed unresectable stage III or stage IV metastatic melanoma Metastasis available for surgical resection (about 2 cm3) and residual measurable disease after resection
- ECOG performance status 0-1
- Life expectancy ≥ 3 months
- No significant toxicity from prior treatments
- Adequate renal, hepatic and hematologic function
- Women of childbearing potential (WOCBP) and men in a sexual relationship with a WOCBP must be using an effective method of contraception during treatment and for at least 6 months after completion af treatment.
- Able to comprehend the information given and willing to sign informed consent
- -
Who cannot join
- Other Malignancies, unless followed for ≥ 5 years with no sign of disease, except squamous cell carcinoma or adequately treated carcinoma in situ colli uteri.
- Cerebral metastasis. Patients with previously treated CNS metastases can participate if CNS metastases are surgically removed or treated with stereotactic radiosurgery and stable ≥ 28 days after treatment measured by MRI. Patients with asymptomatic, stable and untreated CNS metastasis can in be included according to investigators and sponsors decision.
- Patients with ocular melanoma
- Severe allergies, history of anaphylaxis or known allergies to the administered drugs.
- Serious medical or psychiatric comorbidity
- Creatinine clearance < 70 ml/min
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- Acute or chronic infection with e.g. HIV, hepatitis, tuberculosis
- Severe and active autoimmune disease
- Pregnant and nursing women
- Need for immunosuppressive treatment, e.g. corticosteroids or methotrexate
- Concomitant treatment with other experimental drugs
- Patients with uncontrolled hypercalcemia
- Less than four weeks since prior systemic antineoplastic treatment at the time of treatment.
- -
Trial locations and contacts
1 site in 1 country.
Denmark1 site
Center for Cancer Immune Therapy, Dept. of Haematology/Oncology
Copenhagen, Herlev, 2730
About this study
Official title: T Cell Therapy in Combination With Peginterferon for Patients With Metastatic Melanoma
Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from the patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 are administered to support T cell activation and proliferation in vivo.
In this trial the therapy is combined with peginterferon (the pegylated form of interferon alpha 2b). Interferon alpha has immunomodulatory effects and is known to upregulate HLA expression on melanoma cells and are hypothesized to synergize with TIL therapy.
- Conditions
- Metastatic Melanoma
- Being tested
- Cyclophosphamide, Fludarabine, TIL infusion, Interleukin-2, Peginterferon alfa-2b
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Cyclophosphamide 60 mg/kg are administered i.v on day -7 and -6
FludarabineDrug
Also called Fludarabinephosphate, Fludara
Fludarabine 25 mg/m2 are administered i.v on day -5 to -1
TIL infusionBiological
Also called T cell infusion
The maximum number of expanded TILs are infused over 30-45 min on day 0
Interleukin-2Drug
Also called IL-2, Proleukin
Interleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days)
Peginterferon alfa-2bDrug
Also called PegIntron
Peginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14.
| Study group | Role | What they receive |
|---|---|---|
| A | Experimental | All patients receive the same treatment.
All patients are hospitalized during treatment (approximately 3 weeks) and receive treatment only once.
The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) on day -7 to day -1.
The TILs are infused on day 0 and Interleukin-2 therapy are administered on day 0 to day 5.
Interleukin-2 are administered in an i.v. continuous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days
Subcutaneous injections of peginterferon alpha 2b are administered three time (day -2, day 7 and day 14) Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: TIL infusion; Drug: Interleukin-2; Drug: Peginterferon alfa-2b |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Adverse Events/Serious Adverse Events
Determine the safety of the administration of peginterferon in combination with TIL therapy including lymphodepleting chemotherapy and Interleukin-2 by reporting adverse events according to CTCAE v. 4.0
Measured: 0-24 weeks
Secondary outcomes (4)
Treatment Related Immune Responses
Number of participants with detectable in vitro immune responses in the TIL infusion product using intracellular flow cytometry.
Measured: Up to 12 months
Objective Response Rate
Clinical responses will be evaluated by RECIST 1.1 (Response Criteria In Solid Tumors Criteria version 1.1) and assessed by CT scan. Complete response (CR), disapperance of all lesions; Partial response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Objective response (OR) = CR + PR
Measured: Up to 36 months
Overall Survival
Overall survival (OS), defined as time from treatment initiation to death, described using the Kaplan Meier method
Measured: Up to 36 months
Progression Free Survival
Progression free survival (PFS), defined as the time from treatment initiation to disease progression, relapse or death due to any cause, which ever comes first, will be described with the Kaplan Meier method.
Measured: Up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2015 (estimated)
- Study startNov 2014
- Primary completionJan 2018
- Study completionOct 2018
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 Metastatic MelanomaStudies 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
- 12 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
- Inge Marie Svane, Prof, PhD, MD, Study director, Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, DenmarkRikke Andersen, MD, Principal investigator, Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02379195
- Sponsor's protocol ID
- MM1413
- Status last verified
- Jan 2020
- First submitted
- 27 Feb 2015
- Last updated
- 22 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Borch TH, Andersen R, Ellebaek E, Met O, Donia M, Svane IM. Future role for adoptive T-cell therapy in checkpoint inhibitor-resistant metastatic melanoma. J Immunother Cancer. 2020 Jul;8(2):e000668. doi: 10.1136/jitc-2020-000668.
PubMed 32747469
Study at a glance
From the registry record, last updated by the sponsor on 22 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T Cell Therapy in Combination With Peginterferon for Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT02379195
- Acronym / sponsor ID
- MM1413
- Conditions
- Metastatic Melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Inge Marie SvaneUniversity, hospital or other
- Study start
- Nov 2014 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- Oct 2018 (actual)
- First posted
- 4 Mar 2015 (estimated)
- Results
- Posted 22 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Adoptive T cell therapy with tumor infiltrating lymphocytes (TIL) has achieved impressive clinical results with durable complete responses in patients with metastatic melanoma. The TILs are isolated from the patients own tumor tissue followed by in vitro expansion and activation for around 4-6 weeks. Before TIL infusion the patients receive 1 week of preconditioning chemotherapy with cyclophosphamide and fludarabine. After TIL infusion Interleukin-2 are administered to support T cell activation and proliferation in vivo.
In this trial the therapy is combined with peginterferon (the pegylated form of interferon alpha 2b). Interferon alpha has immunomodulatory effects and is known to upregulate HLA expression on melanoma cells and are hypothesized to synergize with TIL therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| A | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: TIL infusion, Drug: Interleukin-2, Drug: Peginterferon alfa-2bAll patients receive the same treatment. All patients are hospitalized during treatment (approximately 3 weeks) and receive treatment only once. The patients are admitted to hospital day -8 and receive lymphodepleting chemotherapy (cyclophosphamide and fludarabine) on day -7 to day -1. The TILs are infused on day 0 and Interleukin-2 therapy are administered on day 0 to day 5. Interleukin-2 are administered in an i.v. continuous decrescendo regimen starting approximately 6 hours after TIL infusion with a duration of approximately 5 days Subcutaneous injections of peginterferon alpha 2b are administered three time (day -2, day 7 and day 14) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Histologically confirmed unresectable stage III or stage IV metastatic melanoma Metastasis available for surgical resection (about 2 cm3) and residual measurable disease after resection
- ECOG performance status 0-1
- Life expectancy ≥ 3 months
- No significant toxicity from prior treatments
- Adequate renal, hepatic and hematologic function
Key exclusion criteria (14 listed)
- Other Malignancies, unless followed for ≥ 5 years with no sign of disease, except squamous cell carcinoma or adequately treated carcinoma in situ colli uteri.
- Cerebral metastasis. Patients with previously treated CNS metastases can participate if CNS metastases are surgically removed or treated with stereotactic radiosurgery and stable ≥ 28 days after treatment measured by MRI. Patients with asymptomatic, stable and untreated CNS metastasis can in be included according to investigators and sponsors decision.
- Patients with ocular melanoma
- Severe allergies, history of anaphylaxis or known allergies to the administered drugs.
- Serious medical or psychiatric comorbidity
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 |
|---|---|---|
| CyclophosphamideCyclophosphamide 60 mg/kg are administered i.v on day -7 and -6 | Drug | A |
| FludarabineAlso: Fludarabinephosphate, FludaraFludarabine 25 mg/m2 are administered i.v on day -5 to -1 | Drug | A |
| TIL infusionAlso: T cell infusionThe maximum number of expanded TILs are infused over 30-45 min on day 0 | Biological | A |
| Interleukin-2Also: IL-2, ProleukinInterleukin-2 are administered as a continuous i.v. infusion in a decrescendo regimen (18 MIU/m2 IL-2 over 6 hours, 18 MIU/m2 IL-2 over 12 hours, 18 MIU IL-2 over 24 hours followed by 4.5 MIU/m2 IL-2 over another 24 hours for three days) | Drug | A |
| Peginterferon alfa-2bAlso: PegIntronPeginterferon alpha-2b, 3 microgram/kg are administered as subcutaneous injection on day -2, day 7 and day 14. | Drug | A |
Primary outcome
Number of Participants With Adverse Events/Serious Adverse Events
Time frame: 0-24 weeks
Determine the safety of the administration of peginterferon in combination with TIL therapy including lymphodepleting chemotherapy and Interleukin-2 by reporting adverse events according to CTCAE v. 4.0
4 secondary outcomes
Treatment Related Immune Responses
Time frame: Up to 12 months
Objective Response Rate
Time frame: Up to 36 months
Overall Survival
Time frame: Up to 36 months
Progression Free Survival
Time frame: Up to 36 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32747469Borch TH, Andersen R, Ellebaek E, Met O, Donia M, Svane IM. Future role for adoptive T-cell therapy in checkpoint inhibitor-resistant metastatic melanoma. J Immunother Cancer. 2020 Jul;8(2):e000668. doi: 10.1136/jitc-2020-000668.
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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.
Inge Marie Svane, Prof, PhD, MD study director
Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
Rikke Andersen, MD principal investigator
Center for Cancer Immune Therapy, Dept of Hematology/Oncology, Copenhagen University Hospital Herlev, Herlev Ringvej 75, DK-2730 Herlev, Denmark
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 Cyclophosphamide, Fludarabine and TIL infusion in people with Metastatic Melanoma, 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 8 inclusion and 14 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 22 Jan 2020. 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 22 Jan 2020). 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 With Adverse Events/Serious Adverse Events (time frame: 0-24 weeks). 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 NCT02379195, 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 22 Jan 2020.