Clinical trial NCT01433172: Combination Immunotherapy of GM.CD40L Vaccine With CCL21 in Lung Cancer
Official title: A Randomized Phase I/II Trial Using a GM-CSF-Producing and CD40L-Expressing Bystander Cell Line (GM.CD40L) Vaccine in Combination With CCL21 for Patients With Stage IV Adenocarcinoma of the Lung
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Lung Cancer
Adenocarcinoma
Keywords: stage IV
adenocarcinoma
vaccine therapy
immunology
tumor vaccine
colony stimulating factor(CSF)
granulocyte-macrophage colony-stimulating factor (GM-CSF)
CC chemokine ligand 21 (CCL21)
Chemokine [C-C motif] ligand 21 (CCL21)
human leukocyte antigen serotype (HLA)
Lead sponsor: H. Lee Moffitt Cancer Center and Research Institute
Sponsor class: OTHER
Collaborators: name: Bankhead-Coley Florida Biomedical Research Program
name: James and Esther King Biomedical Research Program
First posted: 2011-09-13
Enrollment: 73
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to find out what effects (good and bad) a tumor vaccine used in combination with GM.CD40L and CCL21 have on the patient and their cancer. We also want to find out if the vaccine and the drugs can boost the immune system of these patients and how their immune system reacts, both before and after the vaccine treatment.

Detailed description: The vaccine will be made by mixing two kinds of cells: 1) some lung cancer cells, which have been grown in the lab, and 2) experimental "bystander (present but not taking part in the immune response)" cells. All the cells in the vaccine will be treated with high-dose X-rays to make sure that none of them grow and cause more cancer. The bystander cells are human cells that have been genetically changed to express GM-CSF and CD40L. These are called "GM.CD40L". (That is the original cells, called K562, with the genes for human GM-CSF and CD40L inserted into them). These changes are designed to help boost the participants' immune system to better fight the cancer in their body. GM-CSF is a hormone that is known to stimulate bone marrow to make more white blood cells.

CCL21 is a chemokine (protein) that helps to recruit T cells (a type of white blood cell that helps to protect the body from infections) and leads to hyper-responsive T cells. This leads to heightened immune responses when T cells are exposed to both CCL21 and antigen (a substance that when introduced into the body lead to production of an antibody)-presenting cells (A cell that can "present" antigen in a form that T cells can recognize it ). The induction of a strong cell-mediated immune response is the type of immunity expected to be most involved in controlling cancer cell growth. A randomized trial of a vaccine consisting of the GM.CD40L bystander cells and an equivalent number of allogeneic (taken from different individuals) tumor cells plus or minus CCL21 is proposed.

Eligibility criteria: Inclusion Criteria:

* Histologically confirmed metastatic adenocarcinoma of the lung
* Patients must have received and completed first line therapy
* Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1
* No external beam radiation therapy within 2 weeks of first vaccine administration
* No stereotactic radiation therapy within 3 days of first vaccine
* No targeted therapy within 2 weeks of first vaccine administration
* No immunomodulatory therapy within 2 weeks of first vaccine administration
* No chemotherapy within 4 weeks of first vaccine administration
* During Screening period, no steroid therapy within 4 weeks of first vaccine administration
* Patient's written informed consent
* Adequate organ function (measured within a week of beginning treatment):

  * White blood count (WBC) \> 3,000/mm³ and absolute neutrophil count (ANC) \>/= 1500/mm³
  * Platelets \> 100,000/mm³
  * Hematocrit \> 25%
  * Bilirubin \< 2.0 mg/dL
  * Creatinine \< 2.0 mg/dL, or creatinine clearance \> 60 mL/min
* Patients will be tested for HLA-A0201 as determined by flow cytometry followed by molecular analysis of a peripheral blood specimen; however this result will not be an inclusion criterion.
* Measurable metastatic tumor as defined by standard Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Lesions must be accurately measured in at least one dimension with the longest diameter ≥20 mm. With spiral computed tomography (CT) scan, lesion must be ≥10 mm in at least one dimension.

Exclusion Criteria:

* Symptomatic brain metastasis or Uncontrolled central nervous system (CNS) metastasis will not be permitted.
* Any acute medical problems requiring active intervention
* Current corticosteroid (other than replacement doses in patients who are hypo-adrenal) or other immunosuppressive therapy
* Any other pre-existing immunodeficiency condition (including known human immunodeficiency virus \[HIV\] infection)
* Any known pre-existing autoimmune disorder
* History of a second malignancy within the previous 2 years (except non-melanoma skin cancer and cervical in-situ)
* Patients who have had major surgery without full recovery or major surgery within three weeks of the start of vaccine treatment
* Pregnant or lactating women: Patients in reproductive age must agree to use contraceptive methods for the duration of the study (\*A pregnancy test will be obtained before treatment).
* Eastern Cooperative Oncology Group (ECOG) performance status of 2, 3, or 4
* Patients with other significant diseases or disorders that, in the Investigator's opinion, would exclude them from the study.
* Patients who at the discretion of the investigator are deemed to have rapidly progressive disease

Primary outcomes:
measure: Phase I: Recommend Phase II Dose (RPDII)
timeFrame: Up to 6 Months
measure: Phase II: Progression Free Survival (PFS)
timeFrame: Up to 6 Months
Secondary outcomes:
measure: Response Rate
timeFrame: Up to 12 Months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
Study officials:
affiliation: H. Lee Moffitt Cancer Center and Research Institute
name: Jhanelle Gray, M.D.
role: PRINCIPAL_INVESTIGATOR
References: