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

NCT02327390 | Terminated Phase 1 DMC FDA Drug

• 4 other identifiers: CASE3612NCI-2014-00761CASE 3612P30CA043703
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Stage IIIC Skin Melanoma; Stage IV Melanoma

Outcome Measures

Primary Outcomes (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.

  At least 30 days after last infusion

Secondary Outcomes (2)

• Prevalence of each biomarker in peripheral blood over time

  Up to 1 year

• Clinical response defined by Response Evaluation Criteria In Solid Tumors 1.1

  Up to 1 year

Study Arms (1)

X-ACT lymph node cell dose and schedule

EXPERIMENTAL

All 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)

Procedure: lymph node; Biological: X-ACT

Interventions

lymph node PROCEDURE

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

Also known as: lymph node excisional biopsy

X-ACT lymph node cell dose and schedule

X-ACT BIOLOGICAL

Administered as an IV infusion

Also known as: ex vivo-activated autologous lymph node lymphocytes, X-ACT autologous lymph node lymphocytes

X-ACT lymph node cell dose and schedule

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

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

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Lymph Node Excision

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)

Surgical Procedures, Operative

Study Officials

• Julian Kim

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: December 17, 2014
• First Posted: December 30, 2014
• Study Start: March 17, 2015
• Primary Completion: July 18, 2016
• Study Completion: July 18, 2016
• Last Updated: December 6, 2018

Record last verified: 2018-12

Locations

US (1)