Highly efficient PD-1-targeted CRISPR-Cas9 for tumor-infiltrating lymphocyte-based adoptive T cell therapy.
Christopher Aled Chamberlain, Eric Paul Bennett, Anders Handrup Kverneland...
https://pubmed.ncbi.nlm.nih.gov/35141398Actively Recruiting
Phase 1
Age: 18Years - 75Years
All Genders
ID06783270
T-cell Therapy with CRISPR PD1-edited Tumor Infiltrating Lymphocytes for Patients with Metastatic Melanoma
Led by Inge Marie Svane · Updated on 2025-01-20
10
Participants Needed
1
Research Sites
158 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a new treatment approach for patients with advanced or metastatic melanoma that cannot be operated on. The study focuses on the safety and feasibility of using tumor infiltrating lymphocytes (TILs) that have been genetically modified using CRISPR-Cas9 to silence the PD-1 gene. This treatment is intended for patients who have shown disease progression after standard immunotherapy treatments. The trial is a Phase 1 study aiming to see if these modified TILs, called CRISPR-TILs, can be safely infused back into patients and if the process is feasible. The treatment involves removing tumor tissue from the patient to harvest TILs, which are then expanded in the lab over about six weeks. Unlike conventional TIL therapy, these TILs are edited with CRISPR-Cas9 to silence PD-1 before rapid expansion. Patients also receive lymphodepleting chemotherapy and high-dose interleukin-2 as part of the regimen. The CRISPR-TILs are infused into the patient after these preparatory treatments. The study includes a timeline from surgery to CRISPR-TIL infusion lasting 5 to 10 weeks. Participants will be monitored from their admission through to a second evaluation three months after the CRISPR-TIL infusion to track any treatment-related side effects and assess overall feasibility. Researchers will assess the incidence of adverse events during this period and evaluate patient responses to the therapy. Throughout the study, participants undergo various assessments including tumor measurements, heart function tests, and blood tests to ensure safety and monitor treatment effects. The total study involvement includes the treatment and follow-up phases over several months.
CONDITIONS
Official Title
T-cell Therapy with CRISPR PD1-edited Tumor Infiltrating Lymphocytes for Patients with Metastatic Melanoma
Who Can Participate
Age: 18Years - 75Years
All Genders
Eligibility Criteria
You may qualify if you...
- Histologically confirmed inoperable or metastatic melanoma (stage IIIc or IV).
- Progressive disease after standard treatment with anti-PD-1 checkpoint inhibition or in combination with anti-CTLA-4 checkpoint inhibition.
- Age between 18 and 75 years at informed consent.
- ECOG performance status of 1 or less.
- Fit for tumor resection with at least one lesion larger than 1 cm3 available for surgery.
- At least one measurable tumor parameter per RECIST 1.1 criteria excluding the lesion to be removed.
- Left ventricular ejection fraction (LVEF) of 50% or higher.
- Sufficient organ function including specific blood counts and liver, kidney, and coagulation parameters.
- Signed informed consent.
- Willingness to participate in follow-up and handle potential toxicities.
- CRISPR-TIL as next therapy after tumor resection unless bridging therapy is used with required washout periods.
- Women of childbearing potential must have negative pregnancy tests and agree to use effective contraception during and after treatment.
- Men must be surgically sterile or agree to use contraception or abstinence during and after treatment.
You will not qualify if you...
- Recent treatments prior to tumor resection or lymphodepleting chemotherapy including cytotoxic chemotherapy, small molecules, immune therapy, corticosteroids above 10 mg prednisone equivalent, investigational treatments, and certain radiotherapies with specified washout periods.
- Prior T-cell therapy including gene therapy using integrating vectors.
- History of other malignancies unless disease-free for at least 2 years, with exceptions for certain skin and breast cancers.
- Patients with metastatic ocular, mucosal, or non-cutaneous melanoma (except unknown primary melanoma).
- Unresolved toxicity from previous cancer therapy above Grade 1 except stable or irreversible Grade 2 toxicities.
- More than 2 CNS metastases or symptomatic CNS lesions larger than 1 cm or with edema unless treated and stable for 2 months.
- Conditions preventing high-dose interleukin-2 therapy including certain heart and lung diseases.
- Known hypersensitivity to study drugs or excipients.
- Severe medical conditions such as severe asthma, significant cardiac disease, or poorly controlled diabetes.
- Creatinine clearance (eGFR) below 70 ml/min unless dose adjustment approved.
- Active infections including HIV, hepatitis, or syphilis.
- Severe allergies or history of anaphylaxis.
- Active autoimmune or immune-mediated diseases not resolved or requiring high-dose steroids.
- Pregnant or breastfeeding women.
- Unlikely to comply with study protocol requirements as judged by investigator.
AI-Screening
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Complete this quick 3-step screening to check your eligibility
1
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3
Trial Site Locations
Total: 1 location
1
CCIT-DK
Herlev, Capital Region, Denmark, 2730
Actively Recruiting
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Research Team
J
Joel E Sohlin, MD
I
Inge Marie Svane, MD, phd, prof
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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