AzTrials
AzTrials

Stage III Cutaneous Melanoma AJCC v7Phase 2NCT01807182

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

A Phase 2 study testing Aldesleukin, Cyclophosphamide and Fludarabine Phosphate in people with Stage III Cutaneous Melanoma AJCC v7 and Stage IIIA Cutaneous Melanoma AJCC v7, run by Fred Hutchinson Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Aldesleukin, Cyclophosphamide and Fludarabine Phosphate
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
11 participants
Where
1 siteUnited States
Study dates
20 Aug 2013to 26 Aug 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Step I Inclusion Criteria:
  • 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
Show all 15Show fewer
  • Step II Inclusion Criteria:
  • 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)

Who cannot join

  • Step I Exclusion Criteria:
  • 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)
Show all 37Show fewer
  • 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
  • Step II Exclusion Criteria:
  • 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
  • Calculated creatinine clearance (eGFR) < 60 ml/min; EGFR values can be determined by either MDRD or Cockcroft-Gault equation based on the investigator's discretion
  • AST/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)
  • Clinically significant pulmonary dysfunction (FEV1 < 65% predicted or FVC < 65% of predicted, DLCO (corrected for Hgb) < 50% predicted)
  • 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 EKG requiring drug therapy
  • Ejection fraction < 45%, although any patient with an ejection fraction between 45-49% must receive clearance by a cardiologist to be eligible for Step II of this trial
  • Absolute neutrophil count less than 1000/mm^3
  • Platelet count less than 100,000/mm^3
  • Hemoglobin less than 10.0 g/dl
  • Untreated central nervous system metastases that are either symptomatic or greater than 1 cm at time of therapy; lesions that are > 1cm that have been irradiated and in the opinion of the PI or sub-I no longer represent active disease may be allowed
  • Patients with systemic infections requiring active therapy within 72 hours of lymphodepletion
  • Systemic cancer therapy (standard or experimental), including cytotoxic chemotherapy or IL-2, received less than 4 weeks or checkpoint blocking agents (e.g., cytotoxic T-lymphocyte protein [CTLA]-4 or programmed cell death protein [PD]1/PD-ligand [L]1 inhibitors) received less than 6 weeks prior to lymphodepletion, with the exception of targeted therapies
  • Commercially available, molecularly targeted therapies (e.g., dabrafenib, trametinib, vemurafenib, imatinib) taken within 7 days prior to lymphodepletion
  • Clinically significant autoimmune disorders or conditions of immunosuppression; patients with AIDS or HIV-1 associated complex or known to HIV antibody seropositive or known to be recently PCR+ for hepatitis B or C virus are not eligible for this study; virology testing will be done within 6 months of T cell infusion; the severely depressed or altered immune system found in these patients and the possibility of premature death would compromise study objectives
  • Prior treatment with systemic steroids within 4 weeks prior to lymphodepletion (except for physiologic replacement doses for adrenal insufficiency, premedication for contrast allergies for scans, and for drug fever related to targeted therapy)
  • Any other significant medical or psychological conditions that would make the patient unsuitable candidate for cell therapy at the discretion of the PI

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fred Hutch/University of Washington Cancer Consortium

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: Cellular Adoptive Immunotherapy Using Autologous Tumor-Infiltrating Lymphocytes Following Lymphodepletion With Cyclophosphamide and Fludarabine for Patients With Metastatic Melanoma

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.

Read the detailed description

OUTLINE:

Patients receive cyclophosphamide intravenously (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.

After completion of study treatment, patients are followed up at 6, 12, and 24 weeks.

Being tested
Aldesleukin, Cyclophosphamide, Fludarabine Phosphate, Laboratory Biomarker Analysis, Therapeutic Tumor Infiltrating Lymphocytes
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given IV

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative studies

  • Therapeutic Tumor Infiltrating LymphocytesBiological

    Also called Tumor Infiltrating Lymphocytes

    Undergo TIL infusion

Study groups in NCT01807182
Study groupRoleWhat they receive
Treatment (TIL, combination chemotherapy, aldesleukin)ExperimentalPatients 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.
Receives: Biological: Aldesleukin; Drug: Cyclophosphamide; Drug: Fludarabine Phosphate; Other: Laboratory Biomarker Analysis; Biological: Therapeutic Tumor Infiltrating Lymphocytes

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: Up to 24 weeks post infusion

Secondary outcomes (3)

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

    Whole exome and RNA sequencing of tumor cells and normal tissue was performed to identify non synonymous missense mutations, which was then used to generate peptide pools to identify neoantigen-reactive T cells. T-Cell Receptor (TCR) sequencing of T cell clonotypes in blood at time of treatment, 10 months and 24 months was performed and used to assess the persistence of a tumor antigen specific clonotype infused in the TIL product.

    Measured: Up to 24 months

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

    Measured: 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.

  3. A Count of Participants With Biomarker Expression Above Threshold

    Several biomarkers, CXCL13+ CD4 cells, CXCL13+ CD8+ cells, and regulatory cells were evaluated to assess correlation with clinical responses to TIL therapy.

    Measured: Up to 24 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Mar 2013 (estimated)
  2. Study start20 Aug 2013
  3. Primary completion26 Aug 2021
  4. Study completion26 Aug 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
11 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01807182
Sponsor's protocol ID
2643.00
Other IDs
NCI-2013-00486, 2643.00, P30CA015704, RG9213019
Status last verified
Oct 2022
First submitted
6 Mar 2013
Last updated
10 Nov 2022
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Aldesleukin, Cyclophosphamide and Fludarabine Phosphate in people with Stage III Cutaneous Melanoma AJCC v7 and Stage IIIA Cutaneous Melanoma AJCC v7, run by Fred Hutchinson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 10 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Nov 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants in Each Clinical Response Category (time frame: Up to 24 weeks post infusion). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01807182.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Nov 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in