Clinical trial NCT01883323: Tumor-Infiltrating Lymphocytes And Low-Dose Interleukin-2 Therapy Following Cyclophosphamide And Fludarabine In Patients With Melanoma
Official title: Phase II Study Evaluating The Infusion Of Autologous Tumor-Infiltrating Lymphocytes (TILs) And Low-Dose Interleukin-2 (IL-2) Therapy Following A Preparative Regimen Of Non-Myeloablative Lymphodepletion Using Cyclophosphamide And Fludarabine In Patients With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic, Stage III or Stage IV, Melanoma
Keywords: Measurable
Unresectable
Stage III
Stage IV
Metastatic
Melanoma
Tumor-Infiltrating Lymphocytes
Low-Dose Interleukin-2
Cyclophosphamide
Fludarabine
Lead sponsor: University Health Network, Toronto
Sponsor class: OTHER
First posted: 2013-06-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a phase II clinical study for patients with metastatic (the cancer has spread to other parts of the body) melanoma. Patients will receive an infusion (given by vein) of autologous tumor infiltrating lymphocytes (TILs). TILs are a type of white blood cells that recognizes tumor cells and enter them which causes the tumor cells to break down.

Prior to the cell infusion, patients will receive a two drugs cyclophosphamide and fludarabine to prepare the body to receive the TILs. After cell infusion, patients will receive low-dose interleukin-2 therapy which is an approved drug to treat melanoma. This study will see how useful this regimen is in treating metastatic melanoma.


Eligibility criteria: Inclusion Criteria (Eligibility for TIL Evaluation):

* Must have measurable, unresectable stage III or stage IV melanoma
* Suitable tumor for collection
* If tumor is suitable for collection, patient must be suitable for surgery
* Patient must be 18 years of age or older
* Performance status of ECOG 0 or 1
* Life expectancy \> 5 months from date of consent of TIL evaluation
* Willing to be tested for transmissible diseases
* For patients with a history of allergy to penicillin, gentamycin, streptomycin, or anti-fungals, the ability to generate TILs will be confirmed with the cell manufacturing laboratory

Inclusion Criteria (Eligibility for Treatment):

* Signed and dated the informed consent
* No brain metastases or stable brain metastases for 3 months following definitive treatment.
* Life expectancy \> 3 months from the date of consent for TILs treatment
* TILs are suitable for use as determined by laboratory
* More than 30 days since any prior systemic therapy at the time of the cell infusion, or more than six weeks since prior nitrosurea therapy. For patients with prior ipilimumab therapy, at least six weeks must elapse between the last ipilimumab dose and the start of study treatment. All side effects from previous treatment must have recovered to an acceptable grade level.
* Adequate organ function
* Must have positive EBV titres
* Women of child-bearing potential must have a negative pregnancy test. Patients of both genders must be willing to practice birth control during treatment and for 6 months post completion of IL-2 treatment.

Exclusion Criteria:

* Requiring systemic steroid therapy
* HIV positive
* With active hepatitis B or hepatitis C, syphilis, or HTLV
* Must not have any active systemic infections, coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, uncontrolled psychiatric disorders, or other conditions that may affect following study procedures.
* Have no active underlying cardiac illnesses defined by positive stress test, LVEF\<40% or ongoing life-threatening arrhythmias
* Abnormal lung function test

Primary outcomes:
measure: Clinical response to treatment
timeFrame: 6 weeks after treatment
Secondary outcomes:
measure: Number occurrences and severity of side effects
timeFrame: Starting at first dose of study treatment up to 10 years
measure: Number of patients with an immunity and no immunity to the study treatment
timeFrame: From start of study up to 10 years
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
Study officials:
affiliation: Princess Margaret Cancer Centre
name: Butler Marcus, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Nguyen LT, Saibil SD, Sotov V, Le MX, Khoja L, Ghazarian D, Bonilla L, Majeed H, Hogg D, Joshua AM, Crump M, Franke N, Spreafico A, Hansen A, Al-Habeeb A, Leong W, Easson A, Reedijk M, Goldstein DP, McCready D, Yasufuku K, Waddell T, Cypel M, Pierre A, Zhang B, Boross-Harmer S, Cipollone J, Nelles M, Scheid E, Fyrsta M, Lo CS, Nie J, Yam JY, Yen PH, Gray D, Motta V, Elford AR, DeLuca S, Wang L, Effendi S, Ellenchery R, Hirano N, Ohashi PS, Butler MO. Phase II clinical trial of adoptive cell therapy for patients with metastatic melanoma with autologous tumor-infiltrating lymphocytes and low-dose interleukin-2. Cancer Immunol Immunother. 2019 May;68(5):773-785. doi: 10.1007/s00262-019-02307-x. Epub 2019 Feb 11.