In Vivo Persistence of Adoptively-Transferred TIL Cultured With Akti in People With Metastatic Melanoma

NCT02489266 | Withdrawn Phase 1

• 2 other identifiers: 15015315-C-0153
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background: \- One cancer therapy involves taking white blood cells from a person, changing them in a lab, and then giving the cells back to the person. These cells are called tumor infiltrating lymphocytes (TIL). Researchers want to grow some of the TIL cells with the drug Akti to see if they live longer than those grown without it. Objectives: \- To see if TIL cells grown with Akti live longer than those grown without it. Eligibility: \- Adults 18 70 with metastatic melanoma Design:

• Participants will:
• Be screened with tests including scans, x-rays, heart and lung tests, blood and urine tests, and a \<TAB\>possible colonoscopy.
• Have tumor surgery or biopsy.
• Have a large catheter inserted into a vein in the upper chest.
• Receive leukapheresis for 4 5 hours. Blood is removed through a needle in an arm. White blood cells \<TAB\>are removed. The rest of the blood is returned by needle in the other arm.
• The cells will be changed in a laboratory.
• Participants will check into the hospital and:
• For 5 days, get 1 2 chemotherapy drugs by catheter.
• For 1 3 days, get the changed cells by catheter.
• For several days, get 2 drugs to stimulate cells, one by injection, the other by catheter.
• For 7 12 days, recover in the hospital.
• After treatment, participants will:
• Take an antibiotic and antiviral for at least 6 months.
• Return to NIH for several 2-day visits for a few years. At each visit, participants will have lab tests, imaging studies, and a physical exam. At some visits, they may have leukapheresis or blood tests.

Conditions

Metastatic Melanoma

Keywords

Melanoma; Immunotherapy

Outcome Measures

Primary Outcomes (1)

• Determine whether ACT using TIL cultured in a pharmacologic inhibitor of AktKT (during ex vivo expansion) results in enhanced in vivo persistence of TIL after adoptive transfer into autologous patients with advanced melanoma.

  4 years

Secondary Outcomes (2)

• Determine whether ACT using a combination of conventional and AKTi-treated TIL can mediate tumor regression by RECIST guidelines in patients with advanced melanoma

  4 years

• Determine the toxicity profile of this treatment regimen.

  4 years

Study Arms (1)

Arm 1

EXPERIMENTAL

Patients will receive cyclophosphamide and fludarabine followed by infusion of the AKTi-treated TIL, followed by high dose aldesleukin.

Biological: AKTi-treated TIL; Drug: Cyclophosphamide; Drug: Fludarabine; Drug: Aldesleukin

Interventions

AKTi-treated TIL BIOLOGICAL

On day 0, cells will be infused intravenously (IV) over 20-30 minutes (between 1 and 4 days after the last dose of fludarabine).

Arm 1

Cyclophosphamide DRUG

Patients will receive Cyclophosphamide 60 mg/kg/day x 2 days.

Arm 1

Fludarabine DRUG

Patients will receive Fludarabine 25 mg/m2/day for 5 days.

Arm 1

Aldesleukin DRUG

Aldesleukin 720,000 IU/kg IV (based on total body weight) over 15 minutes approximately every 8 hours beginning within 24 hours of cell infusion and continuing for up to 5 days (maximum of 15 doses).

Arm 1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Measurable metastatic melanoma with at least one lesion that is resectable for TIL generation, plus one other lesion that can be measured.
• Confirmation of diagnosis of metastatic melanoma by the Laboratory of Pathology of NCI.
• 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.
• Prior therapy with at least one first line standard therapy including check point inhibitors such as pembrolizumab, nivolumab, or ipilimumab.
• Note: Six weeks must have elapsed from the time of any of these prior antibody therapies that could affect an anti-cancer immune response, at the time the patient receives the preparative regimen to allow antibody levels to decline.
• Note: Patients who have previously received ipilimumab and have documented GI toxicity must have a normal colonoscopy with normal colonic biopsies.
• Greater than or equal to 18 years of age and less than or equal to 70 years of age.
• Willing to sign a durable power of attorney.
• Able to understand and sign the Informed Consent Document
• Clinical performance status of ECOG 0 or 1.
• Life expectancy of greater than three months.
• Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after treatment.
• Serology:
• Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus are less responsive to the experimental treatment and more susceptible to its toxicities.)
• Seronegative for hepatitis B antigen, and 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.

You may not qualify if:

• 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 (for e.g.: requiring anti-infective treatment), coagulation disorders or other active major medical illnesses of the cardiovascular, respiratory or immune system, as evidenced by a positive stress thallium or comparable test, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
• Concurrent systemic steroid therapy.
• History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.
• History of coronary revascularization or ischemic symptoms.
• Documented LVEF of less than or equal to 45%, testing is required in patients with:
• Age greater than or equal to 60 years old
• Clinically significant atrial and or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Related Publications (3)

• Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, Citrin DE, Restifo NP, Robbins PF, Wunderlich JR, Morton KE, Laurencot CM, Steinberg SM, White DE, Dudley ME. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011 Jul 1;17(13):4550-7. doi: 10.1158/1078-0432.CCR-11-0116. Epub 2011 Apr 15.

  PMID: 21498393 BACKGROUND

• Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, Wunderlich JR, Nahvi AV, Helman LJ, Mackall CL, Kammula US, Hughes MS, Restifo NP, Raffeld M, Lee CC, Levy CL, Li YF, El-Gamil M, Schwarz SL, Laurencot C, Rosenberg SA. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011 Mar 1;29(7):917-24. doi: 10.1200/JCO.2010.32.2537. Epub 2011 Jan 31.

  PMID: 21282551 BACKGROUND

• Tran E, Turcotte S, Gros A, Robbins PF, Lu YC, Dudley ME, Wunderlich JR, Somerville RP, Hogan K, Hinrichs CS, Parkhurst MR, Yang JC, Rosenberg SA. Cancer immunotherapy based on mutation-specific CD4+ T cells in a patient with epithelial cancer. Science. 2014 May 9;344(6184):641-5. doi: 10.1126/science.1251102.

  PMID: 24812403 BACKGROUND

MeSH Terms

Conditions

Melanoma

Interventions

Cyclophosphamide; fludarabine; aldesleukin

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; 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

Study Officials

• Steven A Rosenberg, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2015
• First Posted: July 3, 2015
• Study Start: June 24, 2015
• Primary Completion: June 29, 2016
• Study Completion: June 29, 2016
• Last Updated: July 27, 2017

Record last verified: 2016-06-29