Adoptive Transfer of Tumor Infiltrating Lymphocytes for Metastatic Uveal Melanoma

STATUS

Recruiting
End date

Dec 3, 2024
participants needed

47
sponsor

Udai Kammula

Send

Updated on 3 June 2022

See if I qualify

platelet count

gilbert's syndrome

metastasis

neutrophil count

alopecia

clinical protocols

metastatic uveal melanoma

Summary

This is a Phase 2 study in which the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous TIL and high-dose aldesleukin in patients with metastatic uveal melanoma will be evaluated.

Metastatic uveal melanoma (UM) carries a poor prognosis with estimated survival of 4-6 months. There are no known effective systemic therapies. Metastatic UM is classified as an "orphan" disease and there are currently few clinical trial options for these patients. Thus, novel systemic approaches are desperately needed.

A recent pilot study has found that administration of autologous tumor infiltrating lymphocytes (TIL) generated from resected metastases can induce objective tumor response and durable complete response in metastatic uveal melanoma patients. These encouraging results require confirmation to determine if this immunotherapy is of future benefit in treating this disease.

Description

STUDY DESIGN

The Phase 2 study will be conducted in conjunction with companion protocol (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) as described below:

Cell Preparation:

Patients with evaluable metastatic uveal melanoma who have lesions that can be resected with minimum morbidity will undergo resection of tumor. TIL will be obtained while enrolled on the companion protocol (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies). Separate tumor procurements may be performed under a protocol to obtain TIL if initial tumor procurements could not successfully generate TIL. The TIL will be grown and expanded for this trial according to standard operating procedures submitted in the IND. The TIL will be assessed for potency by interferon-gamma release.

Treatment Phase:

Once cells exceed the potency requirement and are projected to exceed the minimum number specified in the COA, the patient will be registered on this study and receive the lymphocyte depleting preparative regimen consisting of fludarabine and cyclophosphamide, followed by infusion of up to 2x10^11 lymphocytes (minimum of 1x10^9 cells) and administration of high-dose intravenous aldesleukin. It is anticipated that TIL that meet the COA will not be achievable in approximately 20% of patients who undergo resection. These patients may undergo a second resection to grow TIL, if another suitable lesion exists. Approximately 6 weeks (+/- 2 weeks) after TIL administration, patients will undergo a complete tumor evaluation and evaluation of toxicity and immunologic parameters. Patients will receive one course of treatment. The start date of the course will be the start date of the chemotherapy; the end date will be the day of the first post-treatment evaluation. Patients may undergo a second treatment. Patients will receive no other experimental agents while on this protocol.

Details

Condition	Uveal Neoplasms, Melanoma, Uveal
Treatment	Tumor Infiltrating Lymphocytes (TIL)
Clinical Study Identifier	NCT03467516
Sponsor	Udai Kammula
Last Modified on	3 June 2022

How understandable was the trial content above?

Hard to understand

Easy to understand

Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Measurable metastatic uveal melanoma
	Patients must be co-enrolled on the companion protocol HCC 17-220 (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies) and have available TIL cultures for therapy
	Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible
	Greater than or equal to 18 years of age and less than or equal to age 75
	Able to understand and sign the Informed Consent Document
	Clinical performance status of ECOG 0 or 1
	Life expectancy of greater than three months
	Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after receiving the treatment
	Serology
	Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
	Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative
	Women of child-bearing potential must have a negative pregnancy test because of the
	potentially dangerous effects of the treatment on the fetus
	Hematology
	Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim
	WBC ≥ 3000/mm3
	Platelet count ≥ 100,000/mm3
	Hemoglobin > 8.0 g/dl
	Chemistry
	Serum ALT/AST ≤ to 3.5 times the upper limit of normal
	Serum creatinine ≤ to 1.6 mg/dl
	Total bilirubin ≤ to 2.0 mg/dl, except in patients with Gilbert's Syndrome who must have a total bilirubin less than 3.0 mg/dl
	More than four weeks must have elapsed since any prior systemic therapy at the time
	the patient receives the preparative regimen, and patients' toxicities must
	have recovered to a clinically manageable level (except for toxicities such as
	alopecia or vitiligo). (Note: Patients may have undergone minor surgical
	procedures within the past 3 weeks, as long as all toxicities have recovered
	to grade 1 or less)
Exclusion Criteria
	Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant
	Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease)
	Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities)
	Active systemic infections (e.g.: requiring anti-infective treatment), coagulation disorders or any other active major medical illnesses
	History of clinically significant major organ autoimmune disease
	Concurrent systemic steroid therapy
	History of severe immediate hypersensitivity reaction to any of the agents used in this study
	History of active coronary or ischemic symptoms
	Documented LVEF of less than or equal to 45%; note: testing is required in patients
	with
	Age > 65 years old
	Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block or have a history of ischemic heart disease, chest pain
	Documented FEV1 less than or equal to 60% predicted tested in patients with
	A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years)
	Symptoms of respiratory dysfunction
	Patients who are receiving any other investigational agents

How to participate?

Step 1 Connect with a study center

Select a site
Send a message

You have contacted , on

Your message has been sent to the study team at ,

A copy of the message has been sent to your email

What happens next?

You can expect the study team to contact you via email or phone in the next few days.
Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Primary Contact

0/250

By sending a message, I agree that my data will be sent to a representative for the selected site and processed in accordance with this website's Privacy Policy (see link in footer).

Step 2 Get screened

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

Step 3 Enroll in the clinical study

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Step 4 Get your study results

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Browse trials for

metastatic uveal melanoma

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Edit Delete

Added by •

•

Private

Edit Delete

Reply by • • Private

Edit Delete

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

Enter the passcode

The passcode will expire in None.

Adoptive Transfer of Tumor Infiltrating Lymphocytes for Metastatic Uveal Melanoma