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

NCT ID: NCT01883323

Last Updated: 2019-11-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-30
• Study Completion Date: 2018-04-30

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.

Conditions

Metastatic, Stage III or Stage IV, Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cyclophosphamide and Fludarabine followed by TILs and IL-2

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)

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

i.v., 60mg/kg per day for 2 days

Fludarabine

Intervention Type: DRUG

i.v., 25mg/m2 per day for 5 days

Tumor-Infiltrating Lymphocytes

Intervention Type: BIOLOGICAL

i.v., 1x10\^10 - 1.6x10\^11 cells

Low-Dose Interleukin

Intervention Type: BIOLOGICAL

i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week)

Interventions

Cyclophosphamide

i.v., 60mg/kg per day for 2 days

Intervention Type: DRUG

Fludarabine

i.v., 25mg/m2 per day for 5 days

Intervention Type: DRUG

Tumor-Infiltrating Lymphocytes

i.v., 1x10\^10 - 1.6x10\^11 cells

Intervention Type: BIOLOGICAL

Low-Dose Interleukin

i.v., 125,000 IU/kg subcut per day, for 2 weeks (2 days rest between each week)

Intervention Type: BIOLOGICAL

Other Intervention Names

CYTOXAN, PROCYTOX; FLUDARA; Aldesleukin, Proleukin, Recombinant Human Interleukin 2

Eligibility Criteria

Inclusion Criteria

• 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

• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Butler Marcus, M.D.

Role: PRINCIPAL_INVESTIGATOR

Princess Margaret Cancer Centre

Locations

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

Canada

References

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.

Reference Type: DERIVED

PMID: 30747243 (View on PubMed)

Other Identifiers

TILs-002-MEL

Identifier Type: -

Identifier Source: org_study_id