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Stage IIIC Skin MelanomaPhase 1NCT02327390

Ex Vivo-Activated Lymph Node Lymphocytes in Treating Patients With Stage IIIC-IV Melanoma

A Phase 1 study testing lymph node and X-ACT in people with Stage IIIC Skin Melanoma and Stage IV Melanoma, run by Case Comprehensive Cancer Center at 1 site in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

This phase I trial studies the safety and best dose of ex-vivo activated lymph node lymphocytes (X-ACT) as well as how well the immune system responds to X-ACT treatment in participants with stage IIIC-IV melanoma. X-ACT treatment involves removing a participant's lymph node(s) close to a melanoma tumor. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Stage IIIC Skin Melanoma, Stage IV Melanoma
What is being tested?
lymph node and X-ACT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
3 participants
Where
1 siteUnited States
Study dates
17 Mar 2015to 18 Jul 2016
Phase
Phase 1
Are there results?
None posted in the registry

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 1
  • Participants must have a histologic diagnosis of melanoma either from a primary or metastatic site; Participants with brain metastases must have completed radiation therapy >30 days prior to enrollment
  • Participants must have American Joint Committee on Cancer (AJCC) stage IIIC unresected or IV disease
  • Patients with non-measureable or measurable disease are eligible. Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter for non-nodal lesions and short axis for nodal lesions to be recorded) as ≥ 20 mm by chest x-ray, as ≥ 10 mm with CT scan, or ≥ 10 mm with calipers by clinical exam. Malignant lymph nodes, to be considered pathologically enlarged and measurable, must be ≥ 15 mm in short axis when assessed by CT scan (CT scan slice thickness recommended to be no greater than 5 mm). At baseline and in follow-up, only the short axis will be measured and followed.
  • Tumor lesions that are situated in a previously irradiated area can be considered measurable as long as ≥ 30 days has passed since radiation to that area
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
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  • Life expectancy (untreated) of > 4 months, in the opinion of and as documented by the investigator
  • White blood count > 3,000/mcL
  • Absolute neutrophil count > 1,200/mcL
  • Platelet count > 100,000/mcL
  • Serum creatinine < 2.0 mg/dL
  • International normalized ratio (INR) ≤ 2.0
  • In the opinion of the investigator, participant must be medically fit to undergo surgical procedure
  • Participants treated with prior chemotherapy, cytotoxic chemotherapy, radiation, biotherapy, or any investigational agent > 30 days prior to lymph node removal are eligible
  • Women of child-bearing potential must agree to use adequate contraception (double barrier method of birth control or abstinence) during participation in the study; should a woman become pregnant or suspect that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately
  • Participants must be disease free of prior invasive malignancies for > 5 years, with the exception of curatively treated basal cell or squamous cell carcinoma of the skin or cancer in-situ of the cervix
  • Participants must be able to understand and willing to sign a written informed consent document
  • STEP 2
  • Successful removal of melanoma-draining lymph node (MDLN)
  • ECOG Performance status ≤ 1
  • White blood count > 3,000/mcL
  • Absolute neutrophil count > 1,500/mcL
  • Platelet count > 100,000/mcL
  • Serum creatinine < 2.0 mg/dL
  • Serum direct bilirubin < 2 x institutional upper limit of normal
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])
  • Alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal
  • Participants with liver metastases who do not meet the eligibility parameters may only be enrolled at the discretion of the principal investigator (PI)

Who cannot join

  • Step 1
  • Participants who are taking immunosuppressive medications that cannot be discontinued (corticosteroids); participants who have discontinued immunosuppressive medications but be at least 1 week post their last dose. Patients who are taking physiologic replacement doses of corticosteroids equivalent to oral prednisone 10 mg per day will not be excluded.
  • Participants who are receiving any other investigational agents
  • Participants with a history of autoimmune disease requiring continuous treatment
  • Participants receiving any medications or substances to treat active infection
  • Pregnant or breastfeeding
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  • Participants with human immunodeficiency virus (HIV) or hepatitis, or known active cytomegalovirus (CMV), Epstein-Barr virus (EBV) or any other viral illness requiring treatment are ineligible because of the potential for pharmacokinetic interactions with ACT lymph node lymphocytes
  • Any condition or behavior that in the judgment of the investigator, would compromise the participant's ability to participate in the study and/or comply with study procedures
  • Patients with bleeding disorders are ineligible due to lymph node removal possibly causing excessive bleeding. Bleeding disorder will be defined by an INR level of > 2.0
  • Step 2 None

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Cleveland Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

    Cleveland, Ohio, 44106-5065

Other trials in United States

About this study

Official title: Phase I Study Using Autologous Ex Vivo-Activated (X-ACT) Lymph Node Lymphocytes as Adoptive Immunotherapy in Advanced Malignant Melanoma Patients

This phase I trial studies the safety and best dose of ex-vivo activated lymph node lymphocytes (X-ACT) as well as how well the immune system responds to X-ACT treatment in participants with stage IIIC-IV melanoma. X-ACT treatment involves removing a participant's lymph node(s) close to a melanoma tumor. These lymph nodes contain special kind of cells (called T cells) which can be activated (getting the cells to start up certain responses in the immune system) outside of the body in an approved laboratory. The activated T cells are then injected back into the same participant using an i.v. to help the participant's immune system to target melanoma. The participant will undergo regular blood testing to determine whether the X-ACT treatment has resulted in changes to the immune system and also whether the T cells which were given back to the patient persist in the blood stream over time. In addition, the effect of the X-ACT treatment on the growth or shrinkage of the participant's melanoma will be measured.

Read the detailed description

PRIMARY OBJECTIVES:

  1. Assess the safety and toxicity profile of repeated infusions of ex-vivo activated tumor-draining lymphocytes (X-ACT) in participants with advanced melanoma.

SECONDARY OBJECTIVES:

  1. Assess the feasibility of multiple infusions of X-ACT. II. Assess the effect of dose and schedule on immunologic parameters using two novel biomarkers.

III. Observe the clinical outcomes of participants receiving X-ACT therapy.

OUTLINE: This is a dose-escalation study.

STEP 1: Participants undergo lymph node biopsy for collection of at least one melanoma-draining lymph node (MDLN). MDLN cells will then be cryopreserved into aliquots until they are needed to generate an activated T cell culture.

STEP 2: Cryopreserved lymph node cells are thawed and then undergo activation with anti-cluster of differentiation (CD)3/anti-CD28 microbeads. The cultures then undergo expansion over 14-18 days in the presence of recombinant human interleukin-2 and anti-vascular endothelial growth factor antibody. The activated X-ACT cells are then transferred i.v. into the same participant from which they were derived with no additional therapy.

Being tested
lymph node, X-ACT
Medical subject headings
Melanoma

What participants receive

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

  • lymph nodeProcedure or surgery

    Also called lymph node excisional biopsy

    Undergo surgery to remove a melanoma-draining lymph node for generation of X-ACT cells in the laboratory

  • X-ACTBiological

    Also called ex vivo-activated autologous lymph node lymphocytes, X-ACT autologous lymph node lymphocytes

    Administered as an IV infusion

Study groups in NCT02327390
Study groupRoleWhat they receive
X-ACT lymph node cell dose and scheduleExperimentalAll patients will begin at dose level 1 and will be moved to higher dosing levels as long as the patient does not experience two or more dose limiting toxicities and maintains an acceptable performance status. A minimum of three patients will be enrolled per dose level and no patients will be enrolled on higher dose levels if dose limiting toxicities are encountered. Dose level 1: 0.5 x 10^10 X-ACT cells. 2 infusions 4 weeks apart Dose level 2: 1.0 x 10^10 X-ACT cells. 1 infusion Dose level 3: 0.5 x 10^10 X-ACT cells. 4 infusions 4 weeks apart Dose level 4: 1.0 x 10^10 X-ACT cells. 2 infusions 4 weeks apart Dose level -1: 0.5 x 10^10 X-ACT cells. 1 infusion (if necessary)
Receives: Procedure: lymph node; Biological: X-ACT

What is being measured

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

  1. Incidence of dose-limiting toxicity

    Number of patients with dose-limiting toxicity will be reported for each treatment group. Maximum tolerated dose may be determined if dose-limiting toxicity is observed.

    Measured: At least 30 days after last infusion

Secondary outcomes (2)

  1. Prevalence of each biomarker in peripheral blood over time

    The temporal profiles of the two biomarkers will be summarized as mean +/- standard deviation at each time point and visualized using scatter plot stratified by dose level and schedule.

    Measured: Up to 1 year

  2. Clinical response defined by Response Evaluation Criteria In Solid Tumors 1.1

    Will be estimated based on the number of clinical responses observed using a binomial distribution and its confidence intervals will be estimated using Wilson's method. A complete response (CR) is defined as the disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to <10mm. A partial response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. Progressive disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm. Stable disease (SD) is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    Measured: Up to 1 year

Timeline

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

  1. First posted30 Dec 2014 (estimated)
  2. Study start17 Mar 2015
  3. Primary completion18 Jul 2016
  4. Study completion18 Jul 2016

Why it stopped: PI Left

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 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
3 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02327390
Sponsor's protocol ID
CASE3612
Other IDs
NCI-2014-00761, CASE 3612, P30CA043703
Status last verified
Dec 2018
First submitted
17 Dec 2014
Last updated
6 Dec 2018
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing lymph node and X-ACT in people with Stage IIIC Skin Melanoma and Stage IV Melanoma, run by Case Comprehensive 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 28 inclusion and 10 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: stopped early, as of the sponsor's last update on 6 Dec 2018. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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

Are results available for this study?

The study was stopped early (reason given: PI Left). Results are not available in the source record.

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?

Incidence of dose-limiting toxicity (time frame: At least 30 days after last 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 NCT02327390.

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 6 Dec 2018.

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