Overview

This trial is active, not recruiting.

Conditions lung cancer, adenocarcinoma
Treatments gm.cd40l.ccl21 vaccinations, gm.cd40l cells vaccinations
Phase phase 1/phase 2
Target CD40
Sponsor H. Lee Moffitt Cancer Center and Research Institute
Collaborator Bankhead-Coley Florida Biomedical Research Program
Start date October 2012
End date June 2017
Trial size 73 participants
Trial identifier NCT01433172, MCC-16439

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Participants enrolled in the Phase I trial will receive GM.CD40L.CCL21 vaccinations on 3 occasions, at 2 week intervals. Note for the phase I portion: the use of steroid medication is to be avoided for 4 weeks prior to the initiation of vaccine therapy and during the vaccine treatment period.
gm.cd40l.ccl21 vaccinations chemokine
This is a dual-agent, phase I study with an expansion of each group at the recommended Phase II dose. Eligible patients are enrolled and the study design and treatment. Eligible patients are entered in cohorts of three at the first dose level. Doses are not escalated over the course of treatment of an individual patient. Patients in Arm B will receive vaccines at the same dose and schedule as described for patients in Arm A. In addition, their vaccine will include H1944 cells expressing CCL21. Note for patients on Arms A and B: the use of steroid medication is to be avoided for 4 weeks before to the initiation of vaccine therapy and during the vaccine treatment period.
(Active Comparator)
Arm A participants will receive GM.CD40L cells vaccinations on 3 occasions, at 2 week intervals. Note on either Arms A and B: the use of steroid medication is to be avoided for 4 weeks before to the initiation of vaccine therapy and during the vaccine treatment period.
gm.cd40l cells vaccinations MHC-negative cell line
Patients randomized to Arm A will receive vaccinations on 3 occasions, at 2 week intervals. 7.5 X 106 irradiated H1944 tumor cells, 7.5 X 106 irradiated H2122 cells, and containing 15 X 106 GM.CD40L cells (1.1 mL) will be injected intradermally into 4 separate sites (0.25 ml injected at each site), in bilateral proximal upper and lower extremities (in the regions of the axillary and inguinal nodal basins). Patients will be restaged approximately 2 weeks after vaccine 3. If patients show no sign of disease progression, patients will then be vaccinated at 4-week intervals.
(Active Comparator)
Arm B participants will receive GM.CD40L.CCL21 vaccinations on 3 occasions, at 2 week intervals. Note on either Arms A and B: the use of steroid medication is to be avoided for 4 weeks before to the initiation of vaccine therapy and during the vaccine treatment period.
gm.cd40l.ccl21 vaccinations chemokine
This is a dual-agent, phase I study with an expansion of each group at the recommended Phase II dose. Eligible patients are enrolled and the study design and treatment. Eligible patients are entered in cohorts of three at the first dose level. Doses are not escalated over the course of treatment of an individual patient. Patients in Arm B will receive vaccines at the same dose and schedule as described for patients in Arm A. In addition, their vaccine will include H1944 cells expressing CCL21. Note for patients on Arms A and B: the use of steroid medication is to be avoided for 4 weeks before to the initiation of vaccine therapy and during the vaccine treatment period.

Primary Outcomes

Measure
Phase I: Recommend Phase II Dose
time frame: Up to 6 Months
Phase II: Progression Free Survival (PFS)
time frame: 6 Months

Secondary Outcomes

Measure
Tumor Response Rate
time frame: Up to 12 Months

Eligibility Criteria

Male or female participants at least 18 years old.

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). - 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

Additional Information

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
Principal investigator Jhanelle Gray, M.D.
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2016.
Information provided to ClinicalTrials.gov by H. Lee Moffitt Cancer Center and Research Institute.
Location data was received from the National Cancer Institute and was last updated in September 2016.