Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers

STATUS

Recruiting
End date

Jun 8, 2033
participants needed

10
sponsor

Udai Kammula

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Updated on 4 October 2022

See if I qualify

platelet count

cancer

fludarabine

cyclophosphamide

immunosuppressive

filgrastim

systemic therapy

minor surgery

squamous cell carcinoma

gilbert's syndrome

metastasis

neutrophil count

brain metastases

alt/ast

hepatitis b antigen

sarcoma

cellular therapy

Summary

This is a Phase 2 study to evaluate the efficacy of a non-myeloablative lymphodepleting preparative regimen followed by infusion of autologous TIL and high-dose aldesleukin in patients with locally advanced, recurrent, or metastatic cancer associated with one of the following cancer types: 1.) gastric/esophagogastric, 2.) colorectal, 3.) pancreatic, 4.) sarcoma, 5.) mesothelioma, 6.) neuroendocrine, 7.) squamous cell cancer, 8.) Merkle cell, 9.) mismatch repair deficient and/or microsatellite unstable cancers, and 10.) patients who have exhausted conventional systemic therapy options by using the objective response rate (ORR).

Description

This 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 locally advanced, recurrent, or metastatic gastric/esophagogastric, colorectal, pancreatic, sarcoma, mesothelioma, neuroendocrine, cutaneous/anal squamous cell, Merkel cell, cancers refractory to systemic therapy, and those with deficient mismatch repair and/or microsatellite instability cancers who have lesions that can be resected or biopsied with minimum morbidity will undergo resection or biopsy of tumor. TIL will be obtained while enrolled on the companion protocol HCC 17-220 (Cell Harvest and Preparation to Support Adoptive Cell Therapy Clinical Protocols and Pre-Clinical Studies). Separate tumor procurements may be performed under HCC 17-220 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	Gastric Cancer, Colorectal Cancer, Pancreatic Cancer, Sarcoma, Mesothelioma, Neuroendocrine Tumors, Squamous Cell Cancer, Merkel Cell Carcinoma, Mismatch Repair Deficiency, Microsatellite Instability
Treatment	Tumor Infiltrating Lymphocytes (TIL), Fludarabine + Cyclophosphamide combination
Clinical Study Identifier	NCT03935893
Sponsor	Udai Kammula
Last Modified on	4 October 2022

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Measurable locally advanced, recurrent, or metastatic cancer associated with one of the
	following cancer types: 1.) gastric/esophagogastric, 2.) colorectal, 3.) pancreatic, 4.)
	sarcoma, 5.) mesothelioma, 6.) neuroendocrine, 7.) squamous cell cancer, 8.) Merkle cell
	) mismatch repair deficient and/or microsatellite unstable cancers, and 10.) patients who
	have exhausted conventional systemic therapy options
	Patients with locally advanced disease should be unresectable by conventional surgical
	approaches
	Patients with distant metastatic spread must have previously received approved first-line
	systemic therapies if they are eligible to receive these treatments
	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
	Patients of both genders who are of child-bearing potential must be willing to practice
	Clinical performance status of ECOG 0 or 1
	birth control from the time of enrollment on this study and for up to four months after
	Life expectancy of greater than three months
	receiving the treatment
	Seronegative for HIV antibody. (The experimental treatment being evaluated in this
	protocol depends on an intact immune system. Patients who are HIV seropositive can
	Serology
	have decreased immune-competence and thus be less responsive to the experimental
	treatment and more susceptible to its toxicities.)
	Seronegative for hepatitis B antigen
	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
	Hematology
	potentially dangerous effects of the treatment on the fetus
	Absolute neutrophil count greater than 1000/mm3 without the support of filgrastim
	WBC ≥ 3000/mm3
	Hemoglobin > 8.0 g/dl
	Platelet count ≥ 100,000/mm3
	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)
	Clinically significant coagulation disorder
	Active major medical illnesses deemed clinically significant by the treating physician
	History of clinically significant major organ autoimmune disease
	Patients with a history of hypothyroidism are eligible
	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
	Clinically significant atrial and or ventricular arrhythmias including but not limited
	Age > 65 years' old
	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
	Symptoms of respiratory dysfunction
	years)
	Patients who are receiving any other investigational agents

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Adoptive Transfer of Tumor Infiltrating Lymphocytes for Advanced Solid Cancers