Metastatic, Stage III or Stage IV, MelanomaPhase 2NCT01883323
Tumor-Infiltrating Lymphocytes And Low-Dose Interleukin-2 Therapy Following Cyclophosphamide And Fludarabine In Patients With Melanoma
A Phase 2 study testing Cyclophosphamide, Fludarabine and Tumor-Infiltrating Lymphocytes in people with Metastatic, Stage III or Stage IV, Melanoma, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
This is a phase II clinical study for patients with metastatic (the cancer has spread to other parts of the body) melanoma. Patients will receive an infusion (given by vein) of autologous tumor infiltrating lymphocytes (TILs). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic, Stage III or Stage IV, Melanoma
- What is being tested?
- Cyclophosphamide, Fludarabine and Tumor-Infiltrating Lymphocytes
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2013to Apr 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have measurable, unresectable stage III or stage IV melanoma
- Suitable tumor for collection
- If tumor is suitable for collection, patient must be suitable for surgery
- Patient must be 18 years of age or older
- Performance status of ECOG 0 or 1
- Life expectancy > 5 months from date of consent of TIL evaluation
Show all 16Show fewer
- Willing to be tested for transmissible diseases
- For patients with a history of allergy to penicillin, gentamycin, streptomycin, or anti-fungals, the ability to generate TILs will be confirmed with the cell manufacturing laboratory
- Signed and dated the informed consent
- No brain metastases or stable brain metastases for 3 months following definitive treatment.
- Life expectancy > 3 months from the date of consent for TILs treatment
- TILs are suitable for use as determined by laboratory
- More than 30 days since any prior systemic therapy at the time of the cell infusion, or more than six weeks since prior nitrosurea therapy. For patients with prior ipilimumab therapy, at least six weeks must elapse between the last ipilimumab dose and the start of study treatment. All side effects from previous treatment must have recovered to an acceptable grade level.
- Adequate organ function
- Must have positive EBV titres
- Women of child-bearing potential must have a negative pregnancy test. Patients of both genders must be willing to practice birth control during treatment and for 6 months post completion of IL-2 treatment.
Who cannot join
- Requiring systemic steroid therapy
- HIV positive
- With active hepatitis B or hepatitis C, syphilis, or HTLV
- Must not have any active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, uncontrolled psychiatric disorders, or other conditions that may affect following study procedures.
- Have no active underlying cardiac illnesses defined by positive stress test, LVEF<40% or ongoing life-threatening arrhythmias
- Abnormal lung function test
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase II Study Evaluating The Infusion Of Autologous Tumor-Infiltrating Lymphocytes (TILs) And Low-Dose Interleukin-2 (IL-2) Therapy Following A Preparative Regimen Of Non-Myeloablative Lymphodepletion Using Cyclophosphamide And Fludarabine In Patients With Metastatic Melanoma
This is a phase II clinical study for patients with metastatic (the cancer has spread to other parts of the body) melanoma. Patients will receive an infusion (given by vein) of autologous tumor infiltrating lymphocytes (TILs). TILs are a type of white blood cells that recognizes tumor cells and enter them which causes the tumor cells to break down.
Prior to the cell infusion, patients will receive a two drugs cyclophosphamide and fludarabine to prepare the body to receive the TILs. After cell infusion, patients will receive low-dose interleukin-2 therapy which is an approved drug to treat melanoma. This study will see how useful this regimen is in treating metastatic melanoma.
- Being tested
- Cyclophosphamide, Fludarabine, Tumor-Infiltrating Lymphocytes, Low-Dose Interleukin
- Keywords
- Measurable, Unresectable, Stage III, Stage IV, Metastatic, Melanoma, Tumor-Infiltrating Lymphocytes, Low-Dose Interleukin-2, Cyclophosphamide, Fludarabine
- Medical subject headings
- Neoplasm Metastasis, Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called CYTOXAN, PROCYTOX
i.v., 60mg/kg per day for 2 days
FludarabineDrug
Also called FLUDARA
i.v., 25mg/m2 per day for 5 days
Tumor-Infiltrating LymphocytesBiological
i.v., 1x10^10 - 1.6x10^11 cells
Low-Dose InterleukinBiological
Also called Aldesleukin, Proleukin, Recombinant Human Interleukin 2
i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week)
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide and Fludarabine followed by TILs and IL-2 | Experimental | Cyclophosphamide, i.v., 60mg/kg per day for 2 days and Fludarabine, i.v., 25mg/m2 per day for 5 days; then Tumor-Infiltrating Lymphocytes, i.v., 1x10^10 - 1.6x10^11 cells and Low-Dose Interleukin, i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week) Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Tumor-Infiltrating Lymphocytes; Biological: Low-Dose Interleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical response to treatment
Measured: 6 weeks after treatment
Secondary outcomes (2)
Number occurrences and severity of side effects
Measured: Starting at first dose of study treatment up to 10 years
Number of patients with an immunity and no immunity to the study treatment
Measured: From start of study up to 10 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2013 (estimated)
- Study startJun 2013
- Primary completionApr 2018
- Study completionApr 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Metastatic, Stage III or Stage IV, MelanomaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Butler Marcus, M.D., Principal investigator, Princess Margaret Cancer Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01883323
- Sponsor's protocol ID
- TILs-002-MEL
- Status last verified
- Nov 2019
- First submitted
- 11 Jun 2013
- Last updated
- 8 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kerr C, Soleimani S, Mulder DT, Nabbi A, Gray D, Pedersen S, Sotov V, Sudhaman S, Nguyen L, Hirano N, Ohashi PS, Butler MO, Pugh TJ. Delineation and monitoring of the T cell repertoire of adoptive cell transfer product during the treatment of advanced melanoma. Genome Med. 2025 Dec 16;18(1):8. doi: 10.1186/s13073-025-01583-w.
PubMed 41402893Nguyen LT, Saibil SD, Sotov V, Le MX, Khoja L, Ghazarian D, Bonilla L, Majeed H, Hogg D, Joshua AM, Crump M, Franke N, Spreafico A, Hansen A, Al-Habeeb A, Leong W, Easson A, Reedijk M, Goldstein DP, McCready D, Yasufuku K, Waddell T, Cypel M, Pierre A, Zhang B, Boross-Harmer S, Cipollone J, Nelles M, Scheid E, Fyrsta M, Lo CS, Nie J, Yam JY, Yen PH, Gray D, Motta V, Elford AR, DeLuca S, Wang L, Effendi S, Ellenchery R, Hirano N, Ohashi PS, Butler MO. Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2. Cancer Immunol Immunother. 2019 May;68(5):773-785. doi: 10.1007/s00262-019-02307-x. Epub 2019 Feb 11.
PubMed 30747243
Study at a glance
From the registry record, last updated by the sponsor on 8 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Study Evaluating The Infusion Of Autologous Tumor-Infiltrating Lymphocytes (TILs) And Low-Dose Interleukin-2 (IL-2) Therapy Following A Preparative Regimen Of Non-Myeloablative Lymphodepletion Using Cyclophosphamide And Fludarabine In Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT01883323
- Acronym / sponsor ID
- TILs-002-MEL
- Keywords
- Measurable, Unresectable, Stage III, Stage IV, Metastatic, Melanoma, Tumor-Infiltrating Lymphocytes, Low-Dose Interleukin-2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Study start
- Jun 2013
- Primary completion
- Apr 2018 (actual)
- Study completion
- Apr 2018 (actual)
- First posted
- 21 Jun 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase II clinical study for patients with metastatic (the cancer has spread to other parts of the body) melanoma. Patients will receive an infusion (given by vein) of autologous tumor infiltrating lymphocytes (TILs). TILs are a type of white blood cells that recognizes tumor cells and enter them which causes the tumor cells to break down.
Prior to the cell infusion, patients will receive a two drugs cyclophosphamide and fludarabine to prepare the body to receive the TILs. After cell infusion, patients will receive low-dose interleukin-2 therapy which is an approved drug to treat melanoma. This study will see how useful this regimen is in treating metastatic melanoma.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cyclophosphamide and Fludarabine followed by TILs and IL-2 | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Biological: Tumor-Infiltrating Lymphocytes, Biological: Low-Dose InterleukinCyclophosphamide, i.v., 60mg/kg per day for 2 days and Fludarabine, i.v., 25mg/m2 per day for 5 days; then Tumor-Infiltrating Lymphocytes, i.v., 1x10^10 - 1.6x10^11 cells and Low-Dose Interleukin, i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Must have measurable, unresectable stage III or stage IV melanoma
- Suitable tumor for collection
- If tumor is suitable for collection, patient must be suitable for surgery
- Patient must be 18 years of age or older
- Performance status of ECOG 0 or 1
Key exclusion criteria (6 listed)
- Requiring systemic steroid therapy
- HIV positive
- With active hepatitis B or hepatitis C, syphilis, or HTLV
- Must not have any active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, uncontrolled psychiatric disorders, or other conditions that may affect following study procedures.
- Have no active underlying cardiac illnesses defined by positive stress test, LVEF<40% or ongoing life-threatening arrhythmias
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 |
|---|---|---|
| CyclophosphamideAlso: CYTOXAN, PROCYTOXi.v., 60mg/kg per day for 2 days | Drug | Cyclophosphamide and Fludarabine followed by TILs and IL-2 |
| FludarabineAlso: FLUDARAi.v., 25mg/m2 per day for 5 days | Drug | Cyclophosphamide and Fludarabine followed by TILs and IL-2 |
| Tumor-Infiltrating Lymphocytesi.v., 1x10^10 - 1.6x10^11 cells | Biological | Cyclophosphamide and Fludarabine followed by TILs and IL-2 |
| Low-Dose InterleukinAlso: Aldesleukin, Proleukin, Recombinant Human Interleukin 2i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week) | Biological | Cyclophosphamide and Fludarabine followed by TILs and IL-2 |
Primary outcome
Clinical response to treatment
Time frame: 6 weeks after treatment
2 secondary outcomes
Number occurrences and severity of side effects
Time frame: Starting at first dose of study treatment up to 10 years
Number of patients with an immunity and no immunity to the study treatment
Time frame: From start of study up to 10 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Nov 2019.
- Derived from this study: PubMed 41402893Kerr C, Soleimani S, Mulder DT, Nabbi A, Gray D, Pedersen S, Sotov V, Sudhaman S, Nguyen L, Hirano N, Ohashi PS, Butler MO, Pugh TJ. Delineation and monitoring of the T cell repertoire of adoptive cell transfer product during the treatment of advanced melanoma. Genome Med. 2025 Dec 16;18(1):8. doi: 10.1186/s13073-025-01583-w.
- Derived from this study: PubMed 30747243Nguyen LT, Saibil SD, Sotov V, Le MX, Khoja L, Ghazarian D, Bonilla L, Majeed H, Hogg D, Joshua AM, Crump M, Franke N, Spreafico A, Hansen A, Al-Habeeb A, Leong W, Easson A, Reedijk M, Goldstein DP, McCready D, Yasufuku K, Waddell T, Cypel M, Pierre A, Zhang B, Boross-Harmer S, Cipollone J, Nelles M, Scheid E, Fyrsta M, Lo CS, Nie J, Yam JY, Yen PH, Gray D, Motta V, Elford AR, DeLuca S, Wang L, Effendi S, Ellenchery R, Hirano N, Ohashi PS, Butler MO. Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2. Cancer Immunol Immunother. 2019 May;68(5):773-785. doi: 10.1007/s00262-019-02307-x. Epub 2019 Feb 11.
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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.
Butler Marcus, M.D. principal investigator
Princess Margaret Cancer Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Cyclophosphamide, Fludarabine and Tumor-Infiltrating Lymphocytes in people with Metastatic, Stage III or Stage IV, Melanoma, run by University Health Network, Toronto at 1 site in Canada.
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 16 inclusion and 6 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 8 Nov 2019. 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 Canada. 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 phase mean?
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Clinical response to treatment (time frame: 6 weeks after treatment). 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 NCT01883323, which also lists 2 linked publications.
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 8 Nov 2019.