Tumor-Infiltrating Lymphocytes After Combination Chemotherapy in Treating Patients With Metastatic Melanoma

NCT01807182 | Completed Phase 2 Results DMC

• 4 other identifiers: 2643.00NCI-2013-00486P30CA015704RG9213019
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies how well tumor-infiltrating lymphocytes (TIL) after combination chemotherapy works in treating patients with melanoma that has spread to other places in the body. Biological therapies, such as TIL, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine phosphate, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving TIL after combination chemotherapy may kill more tumor cells.

Conditions

Stage III Cutaneous Melanoma AJCC v7; Stage IIIA Cutaneous Melanoma AJCC v7; Stage IIIB Cutaneous Melanoma AJCC v7; Stage IIIC Cutaneous Melanoma AJCC v7; Stage IV Cutaneous Melanoma AJCC v6 and v7; Metastatic Melanoma

Outcome Measures

Primary Outcomes (1)

• Number of Participants in Each Clinical Response Category

  Assessed using Response Evaluation Criteria in Solid Tumors 1.1 definitions for complete response, partial response, stable disease, and progressive disease. Clinical response will be determined at 6 weeks, 12 weeks and 24 weeks based on RECIST version 1.137 definitions for Complete Response (CR), Partial Response (PR), Stable Disease (SD) and Progressive Disease (PD). Response reported is best response per participant. A complete response will be defined as total regression of all tumors, a PR as 30% or greater decrease in the sum of the longest diameter of target lesions compared to baseline and PD as 20% increase in the sum of the longest diameter of target lesions compared to the smallest prior diameter (RECIST v1.1 criteria).

  Up to 24 weeks post infusion

Secondary Outcomes (3)

• Number of Participants Who Experienced in Vivo Persistence of Adoptively Transferred T Cells Following TIL Infusion

  Up to 24 months

• Count of Participants Who Experienced Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  Adverse events will be collected through 4 weeks after T cell infusion. Beginning 4 weeks after the T cell infusion, only study-related toxicities will be collected for up to 1 year following T cell infusion.

• A Count of Participants With Biomarker Expression Above Threshold

  Up to 24 weeks

Study Arms (1)

Treatment (TIL, combination chemotherapy, aldesleukin)

EXPERIMENTAL

Patients receive cyclophosphamide IV on days -7 to -6 and fludarabine phosphate IV on days -5 to -1. Patients undergo TIL infusion over 30-60 minutes on day 0 and receive aldesleukin IV every 8 hours on days 1-5 for up to a maximum of 14 doses.

Biological: Aldesleukin; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: Therapeutic Tumor Infiltrating Lymphocytes

Interventions

Aldesleukin BIOLOGICAL

Given IV

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (TIL, combination chemotherapy, aldesleukin)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (TIL, combination chemotherapy, aldesleukin)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (TIL, combination chemotherapy, aldesleukin)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (TIL, combination chemotherapy, aldesleukin)

Therapeutic Tumor Infiltrating Lymphocytes BIOLOGICAL

Undergo TIL infusion

Also known as: Tumor Infiltrating Lymphocytes

Treatment (TIL, combination chemotherapy, aldesleukin)

Eligibility Criteria

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

You may qualify if:

• Stage IV melanoma or stage III melanoma that is unlikely to be cured by surgery
• Able to tolerate high-dose cyclophosphamide, fludarabine and high-dose IL-2
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Patients must have a magnetic resonance imaging (MRI), computed tomography (CT), or positron emission tomography (PET) of the brain within 2 months before consenting if known history of brain metastasis or if clinically indicated; if new lesions are present, principal investigator (PI) or designee should make final determination regarding enrollment
• Patients must have a site of metastatic disease that can be safely resected or biopsied for tissue sufficient for TIL harvest
• Patients must have measurable metastatic melanoma
• Able to tolerate high-dose cyclophosphamide, fludarabine, and high-dose IL-2
• ECOG performance status of 0-1
• Patients must have brain imaging by MRI, CT or PET within 30 days prior to lymphodepletion; patients may have asymptomatic brain lesions that are =\< 1 cm each, lesions that are \> 1 cm that have been irradiated and in the opinion of the investigator no longer represents active disease will also be allowed
• A functional cardiac test (e.g., stress treadmill, stress thallium, multigated acquisition scan (MUGA), dobutamine echocardiogram) to rule out cardiac ischemia within 4 months prior to lymphodepletion is required for all patients
• Pulmonary function tests (PFTs) are required of all patients within 4 months prior to lymphodepletion; forced expiratory volume (FEV)1 and forced vital capacity (FVC) must be \>= 65% predicted and diffusion lung capacity for carbon monoxide (DLCO) must be \>= 50% predicted
• Patients must have their tumor sent for v-Raf murine sarcoma viral oncogene homolog B1(BRAF) mutational analysis
• Patients must have adequate TIL (at least 40 x 10\^6 cells at the pre-expansion stage)

You may not qualify if:

• Men or women of reproductive ability who are unwilling to use effective contraception or abstinence for 4 months after treatment
• Calculated creatinine clearance (estimated glomerular filtration rate \[eGFR\]) \< 60 ml/min; EGFR values can be determined by either Modification of Diet in Renal Disease (MDRD) or Cockcroft-Gault equation based on the investigator's discretion
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \> 3 x upper limit of normal
• Total bilirubin \> 2.0 mg/dl, except in patients with Gilbert's syndrome whose total bilirubin must not exceed 3.0 mg/dl) deemed by investigator to be irreversible
• FEV1 \< 65% predicted, FVC \< 65% of predicted, DLCO (corrected for hemoglobin \[Hgb\]) \< 50% predicted); pulmonary function tests (PFTs) within 4 months prior to consent for Step I will be required for patients with underlying risk factors such as smoking history \> 10 pack years, or a history of pre-existing symptomatic lung disease (not including melanoma metastases to the lung)
• Pre-existing known cardiovascular abnormalities as defined by any one of the following:
• Congestive heart failure
• Clinically significant hypotension
• Cardiac ischemia, or symptoms of coronary artery disease
• Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapy
• Ejection fraction \< 45% (echocardiogram or MUGA), although any patient with an ejection fraction between 45-49% must receive clearance by a cardiologist to be eligible for Step II of the trial
• Clinically significant autoimmune disorders or conditions of immunosuppression; patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 associated complex or known to be HIV antibody seropositive or known to be recently polymerase chain reaction (PCR)+ for hepatitis B or C are not eligible for this study; the severely depressed or altered immune system found in these patients and the possibility of premature death would compromise study objectives
• Patients with active systemic infection requiring intravenous antibiotics
• Clinically significant psychiatric disease which, in the opinion of the PI or sub-investigator (I), would render immunotherapy and its potential sequelae unsafe or compliance with procedural requirements unlikely
• Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within 14 days prior to entry; patients of both genders must practice birth control during treatment and for four months after treatment

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

aldesleukin; Cyclophosphamide; fludarabine phosphate

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

Results Point of Contact

• Title: Dr. Sylvia Lee
• Organization: Fred Hutchinson Cancer Center

smlee@fredhutch.org

206-606-2274

Study Officials

• Sylvia M. Lee

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Program in Immunology

Study Record Dates

• First Submitted: March 6, 2013
• First Posted: March 8, 2013
• Study Start: August 20, 2013
• Primary Completion: August 26, 2021
• Study Completion: August 26, 2021
• Last Updated: November 10, 2022
• Results First Posted: November 10, 2022

Record last verified: 2022-10

Locations

US (1)