Tumor-Infiltrating Lymphocytes And Low-Dose Interleukin-2 Therapy Following Cyclophosphamide And Fludarabine In Patients With Melanoma

University Health Network, Toronto

Status and phase: Completed; Phase 2

Conditions: Metastatic, Stage III or Stage IV, Melanoma

Treatments: Biological: Tumor-Infiltrating Lymphocytes; Drug: Cyclophosphamide; Biological: Low-Dose Interleukin; Drug: Fludarabine

Study type: Interventional

Funder types: Other

Identifiers

NCT01883323

TILs-002-MEL

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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12 participants in 1 patient group

Cyclophosphamide and Fludarabine followed by TILs and IL-2

Experimental group

Description:

Cyclophosphamide, i.v., 60mg/kg per day for 2 days and Fludarabine, i.v., 25mg/m2 per day for 5 days; then Tumor-Infiltrating Lymphocytes, i.v., 1x10\^10 - 1.6x10\^11 cells and Low-Dose Interleukin, i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week)

Treatment:

Drug: Fludarabine

Biological: Tumor-Infiltrating Lymphocytes

Biological: Low-Dose Interleukin

Drug: Cyclophosphamide