Metastatic MelanomaPhase 2NCT01659151
Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer & High Dose IL-2 Metastatic Melanoma
A Phase 2 study testing High Dose Interleukin-2 (IL-2), ACT with TIL Infusion and Vemurafenib in people with Metastatic Melanoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
The purpose of this study is to find out more about the effects of an investigational combination of medicines, which includes special immune cells (T-cells). A T-cell is a type of lymphocyte, or white blood cell. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- High Dose Interleukin-2 (IL-2), ACT with TIL Infusion and Vemurafenib
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Aug 2012to 19 Aug 2025
- Phase
- Phase 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must have unresectable metastatic stage IV melanoma or stage III intransit or regional nodal disease and in the opinion of the PI or treating Coinvestigator is an acceptable candidate for adoptive cell transfer (ACT).
- Residual measurable disease after resection of target lesion(s) for TIL growth
- Tumor must have a B-RAF V600E, D or K mutation by pyrosequencing, Cobas assay, or equivalent (43)
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 - 1. ECOG performance status of 0-1 will be inferred if the patient's level of energy is ≥ 50% of baseline.
- May be treatment-naïve or may have been previously treated for metastatic disease.
- Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within 7 days of starting Vemurafenib.
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- Adequate renal, hepatic and hematologic function, including creatinine of less than or equal to 1.7 gm/dL, total bilirubin less than or equal to 2.0 mg/dL, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dL, aspartic transaminase (AST) and alanine transaminase (ALT) of less than 3X institutional upper limit of normal, hemoglobin of 8 gm/dL or more, white blood count (WBC) of 3000 per mcL and total granulocytes of 1000 per mcL or more, and platelets of 100,000 per mcL or more.
- Must have a positive screening Epstein-Barr Virus (EBV) antibody titre on screening test
- Patients with antibiotic allergies per se are not excluded; although the production of TIL for adoptive transfer includes antibiotics, extensive washing after harvest will minimize systemic exposure to antibiotics.
- At screening, patients with ≤ 3 untreated CNS metastases may be included provided none of the untreated lesions are > 1 cm in greatest dimension, and there is no peri-tumoral edema present on brain imaging (MRI or CT if MRI is contraindicated).
- At screening, patients with ≤ 3 treated central nervous system (CNS) metastases treated with either surgical resection and/or radiation therapy may be included. Patients may be included if the largest lesion is ≤ 1 cm, and there is no evidence of progressive CNS disease on brain imaging at least 28 days after treatment.
- At screening, may be included if the largest lesion is > 1 cm or > 3 in number, and there is no evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy.
- At screening, must have no known history of congenital long QT syndrome and must have a corrected mean QTc interval ≤ 450 msec at baseline.
- No evidence of ongoing cardiac dysrhythmia ≥ grade 2, NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0
- All laboratory and imaging studies must be completed and satisfactory within 30 days of signing the consent document, with the exceptions of: negative serum pregnancy test for WOCBP must be negative within 7 days of starting Vemurafenib, human leukocyte antigen (HLA) typing which will not be repeated if performed previously, and pulmonary function tests/cardiac stress tests whose results are valid for 6 months if performed previously.
Who cannot join
- Patients with active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illness of the cardiovascular, respiratory or immune system, which in the opinion of the principal investigator (PI) or treating co-investigator is not acceptable risk for ACT, are excluded.
- Patients testing positive for HIV titre, Hepatitis B surface antigen, Hepatitis B core antibody, Hepatitis C antibody, human T-cell lymphotropic virus type (HTLV) I or II antibody, or both rapid plasma reagin (RPR) and fluorescent treponemal antibodies (FTA) positive
- Patients who are pregnant or nursing
- Patients needing chronic, immunosuppressive systemic steroids are excluded
- Patients with autoimmune diseases that require immunosuppressive medications
- Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent or render immunotherapy unsafe or contraindicated
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- Patients with > 3 untreated CNS metastases or evidence of peri-tumoral edema
- Patients with ≤ 3 untreated CNS metastases but with at least one lesion >1 cm or peri-tumoral edema
- Patients with congenital long QT syndrome
- Patients with invasive malignancy other than melanoma at the time of enrollment and within 2 years prior to the first Vemurafenib administration are excluded, except for adequately treated (with curative intent) basal or squamous cell carcinoma of the skin, in situ carcinoma of the cervix, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, or limited stage bladder cancer or other cancers from which the patient has been disease-free for at least 2 years.
- Unable to swallow pills
- Patients with treated CNS metastases > 1 cm or > 3 in number will be excluded if there is evidence of progressive CNS disease on brain imaging at least 90 days after treatment with surgery and/or radiation therapy.
- Unable to comprehend and give informed consent
- Previous BRAF inhibitor treatment
- Male patients with female partners of childbearing potential who do not agree to use 2 FDA-accepted forms of contraception during sexual intercourse with women of child-bearing potential from the start of Vemurafenib and up to at least 6 months after discontinuing Vemurafenib
- WOCBP who do not agree to use 2 FDA forms of contraception during sexual intercourse from the start of Vemurafenib and up to at least 6 months after discontinuing Vemurafenib
Trial locations and contacts
1 site in 1 country.
United States1 site
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612
About this study
Official title: A Phase II Clinical Trial of Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Patients With Metastatic Melanoma
The purpose of this study is to find out more about the effects of an investigational combination of medicines, which includes special immune cells (T-cells).
A T-cell is a type of lymphocyte, or white blood cell. Lymphocytes are a kind of white blood cell that protect the body from viral infections, help other cells fight bacterial and fungal infections, produce antibodies, fight cancers, and coordinate the activities of other cells in the immune system.
Read the detailed description
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. They will then be given back to the patient by an infusion in their veins. These cells are called tumor infiltrating lymphocytes (TIL). The investigators want to study the benefits and side effects of TIL when they are given with the following combination of drugs:
- Vemurafenib - a type of drug used to slow the growth of certain types of cancer cells. This drug will be given for about three weeks while T-cells are being grown in the lab and then again after T-cell infusion for up to two years.
- 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 patient's body before they are given the T-cells that were grown in the lab. This is so that there will be more "space" for the lymphocytes (T-cells) 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 they receive the infusion of the T-cells.
The use of TIL is investigational, meaning it has not been approved by the U.S. Food and Drug Administration (FDA). Vemurafenib and IL-2 have been approved by the FDA for the treatment of metastatic melanoma and melanoma that cannot be surgically removed. The chemotherapy drugs fludarabine and cyclophosphamide, used for lymphodepletion, have been approved by the FDA, but not for the treatment of metastatic melanoma.
The combination of vemurafenib followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2 is investigational, and has not been proven to help treat melanoma. This combination is not FDA approved; however, the FDA is allowing its use in this study.
- Conditions
- Metastatic Melanoma
- Being tested
- High Dose Interleukin-2 (IL-2), ACT with TIL Infusion, Vemurafenib, Lymphodepletion
- Keywords
- metastatic, melanoma, cell transfer, ACT, T-cell, immunotherapy, antibodies, lymphocytes
- Medical subject headings
- Melanoma, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High Dose Interleukin-2 (IL-2)Drug
Also called aldesleukin, Proleukin
A high dose regimen of IL-2 will be given after participants receive the infusion of the T-cells.
ACT with TIL InfusionProcedure or surgery
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. They will then be given back to the participant by an infusion in their veins. These cells are called tumor infiltrating lymphocytes (TIL).
VemurafenibDrug
Also called Zelboraf, B-Raf enzyme inhibitor
Vemurafenib is used to slow the growth of certain types of cancer cells. This drug will be given for about 3 weeks while T-cells are being grown in the lab and then again after T-cell infusion for up to 2 years.
LymphodepletionDrug
Also called fludarabine, Fludara, cyclophosphamide, Neostar
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 T-cells that were grown in the lab. This is so that there will be more "space" for the lymphocytes (T-cells) that will be infused in their veins. Fludarabine and cyclophosphamide, 2 types of chemotherapy drugs will be used for what is called lymphodepletion.
| Study group | Role | What they receive |
|---|---|---|
| Combination Therapy | Experimental | Combination Chemotherapy and Immunotherapy. The combination of vemurafenib followed by lymphodepletion with chemotherapy, Adoptive Cell Therapy (ACT) with Tumor Infiltrating Lymphocytes (TIL) infusion, and High Dose Interleukin-2 (IL-2). Receives: Drug: High Dose Interleukin-2 (IL-2); Procedure: ACT with TIL Infusion; Drug: Vemurafenib; Drug: Lymphodepletion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With Overall Response (OR)
Overall response (OR) is defined as the patient being alive at month 12, and tumor size evaluated at screening and at month 12 using the RECIST 1.1 criteria to be a complete response (CR) or partial response (PR). Evaluations will be made by CT scan approximately 12 months from the date of tumor harvest, and by clinical evaluation during the first 12 months
Measured: 12 Months
Percentage of Participant Drop Out Rate
The percentage of participants who drop out due to progression between the time of harvest and TIL transfer (i.e., the "drop-out rate").
Measured: Up to 12 months
Secondary outcomes (1)
Number of Participants With Progression Free Survival (PFS)
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2012 (estimated)
- Study start3 Aug 2012
- Primary completion6 Oct 2021
- Study completion19 Aug 2025
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.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by H. Lee Moffitt Cancer Center and Research InstituteThe 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
- 17 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Amod Sarnaik, M.D., Principal investigator, H. Lee Moffitt Cancer Center and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01659151
- Sponsor's protocol ID
- MCC-16992
- Status last verified
- Feb 2026
- First submitted
- 3 Aug 2012
- Last updated
- 20 Feb 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Clinical Trial of Vemurafenib With Lymphodepletion Plus Adoptive Cell Transfer and High Dose IL-2 in Patients With Metastatic Melanoma
- ClinicalTrials.gov ID
- NCT01659151
- Acronym / sponsor ID
- MCC-16992
- Conditions
- Metastatic Melanoma
- Keywords
- metastatic, melanoma, cell transfer, ACT, T-cell, immunotherapy, antibodies, lymphocytes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Study start
- 3 Aug 2012 (actual)
- Primary completion
- 6 Oct 2021 (actual)
- Study completion
- 19 Aug 2025 (actual)
- First posted
- 7 Aug 2012 (estimated)
- Results
- Posted 3 Feb 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out more about the effects of an investigational combination of medicines, which includes special immune cells (T-cells).
A T-cell is a type of lymphocyte, or white blood cell. Lymphocytes are a kind of white blood cell that protect the body from viral infections, help other cells fight bacterial and fungal infections, produce antibodies, fight cancers, and coordinate the activities of other cells in the immune system.
Detailed description
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. They will then be given back to the patient by an infusion in their veins. These cells are called tumor infiltrating lymphocytes (TIL). The investigators want to study the benefits and side effects of TIL when they are given with the following combination of drugs:
- Vemurafenib - a type of drug used to slow the growth of certain types of cancer cells. This drug will be given for about three weeks while T-cells are being grown in the lab and then again after T-cell infusion for up to two years.
- 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 patient's body before they are given the T-cells that were grown in the lab. This is so that there will be more "space" for the lymphocytes (T-cells) 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 they receive the infusion of the T-cells.
The use of TIL is investigational, meaning it has not been approved by the U.S. Food and Drug Administration (FDA). Vemurafenib and IL-2 have been approved by the FDA for the treatment of metastatic melanoma and melanoma that cannot be surgically removed. The chemotherapy drugs fludarabine and cyclophosphamide, used for lymphodepletion, have been approved by the FDA, but not for the treatment of metastatic melanoma.
The combination of vemurafenib followed by lymphodepletion with chemotherapy, TIL infusion, and high dose IL-2 is investigational, and has not been proven to help treat melanoma. This combination is not FDA approved; however, the FDA is allowing its use in this study.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Combination Therapy | Experimental | Drug: High Dose Interleukin-2 (IL-2), Procedure: ACT with TIL Infusion, Drug: Vemurafenib, Drug: LymphodepletionCombination Chemotherapy and Immunotherapy. The combination of vemurafenib followed by lymphodepletion with chemotherapy, Adoptive Cell Therapy (ACT) with Tumor Infiltrating Lymphocytes (TIL) infusion, and High Dose Interleukin-2 (IL-2). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Must have unresectable metastatic stage IV melanoma or stage III intransit or regional nodal disease and in the opinion of the PI or treating Coinvestigator is an acceptable candidate for adoptive cell transfer (ACT).
- Residual measurable disease after resection of target lesion(s) for TIL growth
- Tumor must have a B-RAF V600E, D or K mutation by pyrosequencing, Cobas assay, or equivalent (43)
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 - 1. ECOG performance status of 0-1 will be inferred if the patient's level of energy is ≥ 50% of baseline.
- May be treatment-naïve or may have been previously treated for metastatic disease.
Key exclusion criteria (16 listed)
- Patients with active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illness of the cardiovascular, respiratory or immune system, which in the opinion of the principal investigator (PI) or treating co-investigator is not acceptable risk for ACT, are excluded.
- Patients testing positive for HIV titre, Hepatitis B surface antigen, Hepatitis B core antibody, Hepatitis C antibody, human T-cell lymphotropic virus type (HTLV) I or II antibody, or both rapid plasma reagin (RPR) and fluorescent treponemal antibodies (FTA) positive
- Patients who are pregnant or nursing
- Patients needing chronic, immunosuppressive systemic steroids are excluded
- Patients with autoimmune diseases that require immunosuppressive medications
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 |
|---|---|---|
| High Dose Interleukin-2 (IL-2)Also: aldesleukin, ProleukinA high dose regimen of IL-2 will be given after participants receive the infusion of the T-cells. | Drug | Combination Therapy |
| ACT with TIL InfusionSpecial 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. They will then be given back to the participant by an infusion in their veins. These cells are called tumor infiltrating lymphocytes (TIL). | Procedure or surgery | Combination Therapy |
| VemurafenibAlso: Zelboraf, B-Raf enzyme inhibitorVemurafenib is used to slow the growth of certain types of cancer cells. This drug will be given for about 3 weeks while T-cells are being grown in the lab and then again after T-cell infusion for up to 2 years. | Drug | Combination Therapy |
| LymphodepletionAlso: fludarabine, Fludara, cyclophosphamide, NeostarThe 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 T-cells that were grown in the lab. This is so that there will be more "space" for the lymphocytes (T-cells) that will be infused in their veins. Fludarabine and cyclophosphamide, 2 types of chemotherapy drugs will be used for what is called lymphodepletion. | Drug | Combination Therapy |
Primary outcome
Percentage of Participants With Overall Response (OR)
Time frame: 12 Months
Overall response (OR) is defined as the patient being alive at month 12, and tumor size evaluated at screening and at month 12 using the RECIST 1.1 criteria to be a complete response (CR) or partial response (PR). Evaluations will be made by CT scan approximately 12 months from the date of tumor harvest, and by clinical evaluation during the first 12 months
Percentage of Participant Drop Out Rate
Time frame: Up to 12 months
The percentage of participants who drop out due to progression between the time of harvest and TIL transfer (i.e., the "drop-out rate").
1 secondary outcome
Number of Participants With Progression Free Survival (PFS)
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Feb 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Amod Sarnaik, M.D. principal investigator
H. Lee Moffitt Cancer Center and Research Institute
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 High Dose Interleukin-2 (IL-2), ACT with TIL Infusion and Vemurafenib in people with Metastatic Melanoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
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 15 inclusion and 16 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 20 Feb 2026. 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 United States. 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?
Yes. Results are posted in the registry (first posted 3 Feb 2022). 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?
Percentage of Participants With Overall Response (OR) (time frame: 12 Months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Feb 2026.