MelanomaPhase 1/2NCT06961357
Clinical Trial of CD40L-augmented TIL for Patients With Advanced Melanoma
A Phase 1/2 study testing Cyclophosphamide, Fludarabine and Interleukin-2 in people with Melanoma, run by H. Lee Moffitt Cancer Center and Research Institute at 1 site in United States.
Trial summary
This is a phase I/II clinical trial of a single dose of CD40L-augmented TIL administered in patients with advanced melanoma (Cohort 1: Cutaneous acral melanoma, cutaneous non-acral melanoma, (n=26); Cohort 2: Mucosal melanoma, uveal melanoma, (n=10)). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Melanoma
- What is being tested?
- Cyclophosphamide, Fludarabine and Interleukin-2
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Dec 2025to May 2030
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
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
- Participants must have histologically confirmed, unresectable (Stage III/IV) or metastatic melanoma as follows: Cutaneous, non-acral, melanoma (including melanoma of unknown primary); Cutaneous acral melanoma; Mucosal melanoma; Ocular melanoma (including uveal, iris, conjunctival melanoma).
- Participants must have failed, be refractory to, or unable to tolerate at least one line of standard of care in the opinion of the Investigator. For participants with cutaneous non-acral melanoma, standard of care therapy includes a PD-1/L1 or combination therapy with anti-PD1 and anti-CTLA4 or combination therapy of anti-PD1 and anti-LAG3 or if BRAF V600 activating mutation positive, a BRAF ± MEK inhibitor. Participants are allowed to be enrolled in this trial if they failed one line of any of those standards of care therapy regimens.
- Any systemic therapy, including anti-cancer monoclonal antibodies, must have been completed at least 4 weeks from the start of lymphodepleting therapy, and any prior therapy-related AEs must have resolved to Grade ≤ 1 except for alopecia and vitiligo.
- Participants must be ages ≥18. Additionally, participants who are ≥ 65 years of age may need to undergo a cardiology evaluation including a cardiac stress test or coronary computed tomography after which they must be deemed to be low/acceptable risk. This cardiac evaluation may be omitted for patients who underwent testing within 6 months and have no interval change in cardiopulmonary clinical status. Note 1: Cardiac stress test may be omitted for patients ≥65 years old (y/o) who are fully functional with no relevant medical comorbidities and are able to carry ≥4 METS activities at baseline. For patients who demonstrate abnormal cardiac stress test cardiac evaluation by cardiologist will be done and if deemed low acceptable risk, will be allowed to participate in this trial per PI discretion. Cardiac stress test may be indicated for any patient <65 y/o who have relevant medical comorbidities or demonstrate clinically worrisome symptoms. Note 2: While age preference will be between 18-75 years, this study allows age >75 years if the patient meets eligibility criteria and demonstrates no significant medical comorbidities per PI.
- ECOG performance status of 0 or 1.
- Participants must have adequate organ and marrow function as defined within the protocol.
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- Seronegative for Human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, and hepatitis C (HCV) antibody (if HCV antibody positive, must be tested for HCV RNA, which must be negative to be eligible).
- Participants with brain metastases are eligible provided that the brain metastases have been successfully treated with stereotactic radiosurgery or resection and clinically stable for at least 4 weeks (±14 days). Note: Participants who develop brain metastases after tumor harvest and/or lymphodepleting therapy will be allowed to remain on study and may proceed with cell therapy after undergoing definitive radiation therapy and/or surgery. For those participants who develop brain metastases during lymphodepleting therapy and undergo definitive radiation therapy and/or surgery careful decision will be made to proceed with TIL infusion after discussion with treating physician, neurosurgeon, radiation oncologist and PI.
- Women of child-bearing potential must have a negative pregnancy test.
- The effects of CD40L-augmented TIL on the developing human fetus are unknown. For this reason and because TIL agents, as well as other therapeutic agents used in this trial including IL-2 are known to be teratogenic, both males and females of childbearing potential must be willing to practice birth control starting with screening through 1 year after the last study drug is administered for females or 6 months for males.
- Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study, she should inform her treating physician immediately.
- Ability to understand and the willingness to sign a written informed consent document.
- Participants should have at least one surgically accessible lesion for tumor harvest for preparation of TIL, and at least one RECIST v1.1 measurable lesion after tumor harvest to follow for response assessment. Note: Tumor harvest lesion will be considered as target lesion if after harvest remaining portion of tumor meets RECIST v1.1 measurable lesion criteria.
Who cannot join
- Participants, regardless of age, who have a current or past medical history of ischemic heart disease, or clinically significant atrial or ventricular rhythm abnormality are excluded unless they undergo a cardiac stress test and cardiology clearance examination and are determined to be low or acceptable risk.
- Participants with either a primary immunodeficiency disorder (i.e., severe combined immunodeficiency syndrome) or acquired immunodeficiency disorders (such as HIV/AIDS).
- Pregnant women are excluded from this study because the agents used in this study have teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CD40L-augmented TIL or the other agents in the study, breastfeeding should be discontinued if the mother is enrolled in the study.
- Participants taking systemic steroid therapy (other than replacement therapy or prednisone equivalent of ≤10mg daily) or therapy with any immunosuppressive medications such as mycophenolate mofetil (MMF). Participants who require more than 10mg of prednisone or equivalent other steroid therapy should taper their steroid therapy to 10 mg prednisone 1 week prior to planned first interventional drug therapy (lymphodepleting therapy). Participants who are on baseline replacement therapy or prednisone equivalent of ≤10mg daily and require stress doses of steroid therapy will be allowed to receive stress dose steroids during the trial interventions. Participants who require dapsone for pneumocystis pneumonia (PCP) prophylaxis during TIL therapy are eligible.
- Participants who have a history of severe immediate hypersensitivity reaction to the study agents including cyclophosphamide, fludarabine, or IL-2 or any of their constituents.
- Participants with a left ventricular ejection fraction (LVEF) ≤ 45% or New York Heart Association (NYHA) functional classification > 1.
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- Forced expiratory volume (FEV1) ≤ 60% of predicted value and DLCO (corrected) < 60% of predicted value. Participants who underwent pulmonary function testing within 6 months of screening may omit PFTs if they demonstrate stable cardiopulmonary status.
- Participants who, in the opinion of the Investigator, have a medical condition that would subject the patient to prohibitive risk by participation in this study, or who may be unable to safely complete tumor harvest, lymphodepletion regimen, TIL infusion, or aldesleukin administration.
- Participants with active infections requiring antibiotics.
- Participants with active autoimmune diseases currently requiring systemic treatment with immunosuppressive doses of corticosteroids (>10 mg of prednisone-equivalent daily dosing), immunosuppressive biologic agents, or disease modifying antirheumatic drug agents (DMARDs).
- Patients who received prior live cell therapy are excluded, unless express written permission is provided by the clinical PI.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Moffitt Cancer Center
Tampa, Florida, 33612
Lilit Karapetyan, MD
About this study
Official title: Phase I/II Clinical Trial of CD40L-augmented Tumor Infiltrating Lymphocytes (TIL) for Patients With Advanced Melanoma
This is a phase I/II clinical trial of a single dose of CD40L-augmented TIL administered in patients with advanced melanoma (Cohort 1: Cutaneous acral melanoma, cutaneous non-acral melanoma, (n=26); Cohort 2: Mucosal melanoma, uveal melanoma, (n=10)). Patients will undergo an excision of a readily accessible tumor for preparation of TIL. Eligible patients with progressive disease after standard of care therapy will undergo lymphodepletion with cyclophosphamide and fludarabine followed by CD40L-augmented TIL and standard of care bolus dose interleukin-2 (short-course IL-2).
- Conditions
- Melanoma
- Being tested
- Cyclophosphamide, Fludarabine, Interleukin-2, TIL Product
- Keywords
- Mucosal melanoma, Uveal melanoma, Cutaneous acral melanoma, Cutaneous non-acral melanoma
- Medical subject headings
- Melanoma, Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Part of lymphodepletion regimen.
FludarabineDrug
Part of lymphodepletion regimen.
Interleukin-2Drug
Standard of care.
TIL ProductDrug
Tumor-infiltrating lymphocytes are an investigational, personalized adoptive cell therapy.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1: Phase I safety trial | Experimental | Participants will receive a single dose of CD40L-Augmented TIL. Toxicity will be evaluated at every 4 patients. The study may enroll 16-20 patients to reach 12 TIL safety evaluable patients. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2; Drug: TIL Product |
| Cohort 1: Phase II efficacy trial | Experimental | If there are 2 responders or more, the trial will continue to enroll additional 14 patients in the 2nd stage. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2; Drug: TIL Product |
| Cohort 2: Rare melanoma subtypes | Experimental | Cohort 2 will include n=10 patients with the rare melanoma histological subtypes of mucosal or uveal melanoma and will be used to assess feasibility and toxicity of the treatment in those rare melanoma subtypes. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2; Drug: TIL Product |
| Cohort 3: TIL derived from core needle biopsy samples (all subtypes) | Experimental | Cohort 3 will include 12 patients with any subtype of melanoma whose TILs are manufactured from CNB specimens to assess the feasibility of this process. Receives: Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Interleukin-2; Drug: TIL Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase I: Treatment Emergent Adverse Events (TEAE)
The proportion of patients who experience a TEAE
Measured: Up to 28 days post TIL
Phase II: Objective Response Rate
The proportion of response evaluable patients.
Measured: Up to 60 Months
Secondary outcomes (3)
Duration of response
Duration of response (DOR) in months, of the total response-evaluable patients.
Measured: Up to 60 Months
Progression Free Survival (PFS)
Progression Free Survival (PFS) in months of the total safety-evaluable patients, and the total treated patients.
Measured: Up to 60 Months
Overall survival
Overall Survival (OS) in months of the total safety-evaluable patients, and the total treated patients.
Measured: Up to 60 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2025
- Study start3 Dec 2025
- Primary completionMay 2029 (estimated)
- Study completionMay 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lilit Karapetyan, MD, Principal investigator, Moffitt Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06961357
- Sponsor's protocol ID
- MCC-23082
- Status last verified
- Jun 2026
- First submitted
- 29 Apr 2025
- Last updated
- 26 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Clinical Trial of CD40L-augmented Tumor Infiltrating Lymphocytes (TIL) for Patients With Advanced Melanoma
- ClinicalTrials.gov ID
- NCT06961357
- Acronym / sponsor ID
- MCC-23082
- Conditions
- Melanoma
- Keywords
- Mucosal melanoma, Uveal melanoma, Cutaneous acral melanoma, Cutaneous non-acral melanoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- H. Lee Moffitt Cancer Center and Research InstituteUniversity, hospital or other
- Study start
- 3 Dec 2025 (actual)
- Primary completion
- May 2029 (estimated)
- Study completion
- May 2030 (estimated)
- First posted
- 7 May 2025 (actual)
- 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 I/II clinical trial of a single dose of CD40L-augmented TIL administered in patients with advanced melanoma (Cohort 1: Cutaneous acral melanoma, cutaneous non-acral melanoma, (n=26); Cohort 2: Mucosal melanoma, uveal melanoma, (n=10)). Patients will undergo an excision of a readily accessible tumor for preparation of TIL. Eligible patients with progressive disease after standard of care therapy will undergo lymphodepletion with cyclophosphamide and fludarabine followed by CD40L-augmented TIL and standard of care bolus dose interleukin-2 (short-course IL-2).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1: Phase I safety trial | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Interleukin-2, Drug: TIL ProductParticipants will receive a single dose of CD40L-Augmented TIL. Toxicity will be evaluated at every 4 patients. The study may enroll 16-20 patients to reach 12 TIL safety evaluable patients. |
| Cohort 1: Phase II efficacy trial | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Interleukin-2, Drug: TIL ProductIf there are 2 responders or more, the trial will continue to enroll additional 14 patients in the 2nd stage. |
| Cohort 2: Rare melanoma subtypes | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Interleukin-2, Drug: TIL ProductCohort 2 will include n=10 patients with the rare melanoma histological subtypes of mucosal or uveal melanoma and will be used to assess feasibility and toxicity of the treatment in those rare melanoma subtypes. |
| Cohort 3: TIL derived from core needle biopsy samples (all subtypes) | Experimental | Drug: Cyclophosphamide, Drug: Fludarabine, Drug: Interleukin-2, Drug: TIL ProductCohort 3 will include 12 patients with any subtype of melanoma whose TILs are manufactured from CNB specimens to assess the feasibility of this process. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Participants must have histologically confirmed, unresectable (Stage III/IV) or metastatic melanoma as follows: Cutaneous, non-acral, melanoma (including melanoma of unknown primary); Cutaneous acral melanoma; Mucosal melanoma; Ocular melanoma (including uveal, iris, conjunctival melanoma).
- Participants must have failed, be refractory to, or unable to tolerate at least one line of standard of care in the opinion of the Investigator. For participants with cutaneous non-acral melanoma, standard of care therapy includes a PD-1/L1 or combination therapy with anti-PD1 and anti-CTLA4 or combination therapy of anti-PD1 and anti-LAG3 or if BRAF V600 activating mutation positive, a BRAF ± MEK inhibitor. Participants are allowed to be enrolled in this trial if they failed one line of any of those standards of care therapy regimens.
- Any systemic therapy, including anti-cancer monoclonal antibodies, must have been completed at least 4 weeks from the start of lymphodepleting therapy, and any prior therapy-related AEs must have resolved to Grade ≤ 1 except for alopecia and vitiligo.
- Participants must be ages ≥18. Additionally, participants who are ≥ 65 years of age may need to undergo a cardiology evaluation including a cardiac stress test or coronary computed tomography after which they must be deemed to be low/acceptable risk. This cardiac evaluation may be omitted for patients who underwent testing within 6 months and have no interval change in cardiopulmonary clinical status. Note 1: Cardiac stress test may be omitted for patients ≥65 years old (y/o) who are fully functional with no relevant medical comorbidities and are able to carry ≥4 METS activities at baseline. For patients who demonstrate abnormal cardiac stress test cardiac evaluation by cardiologist will be done and if deemed low acceptable risk, will be allowed to participate in this trial per PI discretion. Cardiac stress test may be indicated for any patient <65 y/o who have relevant medical comorbidities or demonstrate clinically worrisome symptoms. Note 2: While age preference will be between 18-75 years, this study allows age >75 years if the patient meets eligibility criteria and demonstrates no significant medical comorbidities per PI.
- ECOG performance status of 0 or 1.
Key exclusion criteria (11 listed)
- Participants, regardless of age, who have a current or past medical history of ischemic heart disease, or clinically significant atrial or ventricular rhythm abnormality are excluded unless they undergo a cardiac stress test and cardiology clearance examination and are determined to be low or acceptable risk.
- Participants with either a primary immunodeficiency disorder (i.e., severe combined immunodeficiency syndrome) or acquired immunodeficiency disorders (such as HIV/AIDS).
- Pregnant women are excluded from this study because the agents used in this study have teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with CD40L-augmented TIL or the other agents in the study, breastfeeding should be discontinued if the mother is enrolled in the study.
- Participants taking systemic steroid therapy (other than replacement therapy or prednisone equivalent of ≤10mg daily) or therapy with any immunosuppressive medications such as mycophenolate mofetil (MMF). Participants who require more than 10mg of prednisone or equivalent other steroid therapy should taper their steroid therapy to 10 mg prednisone 1 week prior to planned first interventional drug therapy (lymphodepleting therapy). Participants who are on baseline replacement therapy or prednisone equivalent of ≤10mg daily and require stress doses of steroid therapy will be allowed to receive stress dose steroids during the trial interventions. Participants who require dapsone for pneumocystis pneumonia (PCP) prophylaxis during TIL therapy are eligible.
- Participants who have a history of severe immediate hypersensitivity reaction to the study agents including cyclophosphamide, fludarabine, or IL-2 or any of their constituents.
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 |
|---|---|---|
| CyclophosphamidePart of lymphodepletion regimen. | Drug | Cohort 1: Phase I safety trial, Cohort 1: Phase II efficacy trial, Cohort 2: Rare melanoma subtypes, Cohort 3: TIL derived from core needle biopsy samples (all subtypes) |
| FludarabinePart of lymphodepletion regimen. | Drug | Cohort 1: Phase I safety trial, Cohort 1: Phase II efficacy trial, Cohort 2: Rare melanoma subtypes, Cohort 3: TIL derived from core needle biopsy samples (all subtypes) |
| Interleukin-2Standard of care. | Drug | Cohort 1: Phase I safety trial, Cohort 1: Phase II efficacy trial, Cohort 2: Rare melanoma subtypes, Cohort 3: TIL derived from core needle biopsy samples (all subtypes) |
| TIL ProductTumor-infiltrating lymphocytes are an investigational, personalized adoptive cell therapy. | Drug | Cohort 1: Phase I safety trial, Cohort 1: Phase II efficacy trial, Cohort 2: Rare melanoma subtypes, Cohort 3: TIL derived from core needle biopsy samples (all subtypes) |
Primary outcome
Phase I: Treatment Emergent Adverse Events (TEAE)
Time frame: Up to 28 days post TIL
The proportion of patients who experience a TEAE
Phase II: Objective Response Rate
Time frame: Up to 60 Months
The proportion of response evaluable patients.
3 secondary outcomes
Duration of response
Time frame: Up to 60 Months
Progression Free Survival (PFS)
Time frame: Up to 60 Months
Overall survival
Time frame: Up to 60 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jun 2026.
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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.
Lilit Karapetyan, MD principal investigator
Moffitt Cancer Center
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 Interleukin-2 in people with 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 13 inclusion and 11 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: looking for participants now, as of the sponsor's last update on 26 Jun 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 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Tina Swartzlander (813-745-5517, Tina.Swartzlander@moffitt.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase I: Treatment Emergent Adverse Events (TEAE) (time frame: Up to 28 days post TIL). 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 26 Jun 2026.