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

NCT01883323 | Completed Phase 2 DMC

• 1 other identifier: TILs-002-MEL
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

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

Keywords

Measurable; Unresectable; Stage III; Stage IV; Metastatic; Melanoma; Tumor-Infiltrating Lymphocytes; Low-Dose Interleukin-2; Cyclophosphamide; Fludarabine

Outcome Measures

Primary Outcomes (1)

• Clinical response to treatment

  6 weeks after treatment

Secondary Outcomes (2)

• Number occurrences and severity of side effects

  Starting at first dose of study treatment up to 10 years

• Number of patients with an immunity and no immunity to the study treatment

  From start of study up to 10 years

Study Arms (1)

Cyclophosphamide and Fludarabine followed by TILs and IL-2

EXPERIMENTAL

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)

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

Interventions

Cyclophosphamide DRUG

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

Also known as: CYTOXAN, PROCYTOX

Cyclophosphamide and Fludarabine followed by TILs and IL-2

Fludarabine DRUG

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

Also known as: FLUDARA

Cyclophosphamide and Fludarabine followed by TILs and IL-2

Tumor-Infiltrating Lymphocytes BIOLOGICAL

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

Cyclophosphamide and Fludarabine followed by TILs and IL-2

Low-Dose Interleukin BIOLOGICAL

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

Also known as: Aldesleukin, Proleukin, Recombinant Human Interleukin 2

Cyclophosphamide and Fludarabine followed by TILs and IL-2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Related Publications (1)

• 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.

  PMID: 30747243 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Melanoma

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Interleukins; aldesleukin

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Butler Marcus, M.D.

  Princess Margaret Cancer Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 11, 2013
• First Posted: June 21, 2013
• Study Start: June 1, 2013
• Primary Completion: April 1, 2018
• Study Completion: April 1, 2018
• Last Updated: November 8, 2019

Record last verified: 2019-11

Locations

CA (1)