Combination Immunotherapy of GM.CD40L Vaccine With CCL21 in Lung Cancer

NCT ID: NCT01433172

Last Updated: 2019-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-26
• Study Completion Date: 2019-02-01

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.

Conditions

Lung Cancer; Adenocarcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase I Vaccinations

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.

Group Type: EXPERIMENTAL

Phase I - GM.CD40L.CCL21 Vaccinations

Intervention Type: BIOLOGICAL

This is a dual-agent, Phase I study with an expansion of each group at the recommended Phase II dose. Participants are entered in cohorts of 3 at the first dose level. Doses are not escalated over the course of treatment of an individual patient.

Phase I: Participants receive the GM.CD40L.CCL21 vaccine in a standard 3+3 design.

Phase II Arm A Vaccinations

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.

Group Type: ACTIVE_COMPARATOR

Phase II - GM.CD40L cells Vaccinations

Intervention Type: BIOLOGICAL

Patients randomized to Arm A will receive vaccinations on 3 occasions, at 2 week intervals. 7.5 X 10\^6 irradiated H1944 tumor cells, 7.5 X 10\^6 irradiated H2122 cells, and containing 15 X 10\^6 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.

Phase II Arm B Vaccinations

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.

Group Type: ACTIVE_COMPARATOR

Phase II - GM.CD40L.CCL21 Vaccinations

Intervention Type: BIOLOGICAL

This is a dual-agent, Phase I study with an expansion of each group at the recommended Phase II dose. Participants are entered in cohorts of 3 at the first dose level. Doses are not escalated over the course of treatment of an individual patient.

Phase II: Participants are randomized to one of the 2 arms (ratio 1:1): GM.CD40L versus GM.CD40L.CCL21. 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.

Interventions

Phase I - GM.CD40L.CCL21 Vaccinations

This is a dual-agent, Phase I study with an expansion of each group at the recommended Phase II dose. Participants are entered in cohorts of 3 at the first dose level. Doses are not escalated over the course of treatment of an individual patient.

Phase I: Participants receive the GM.CD40L.CCL21 vaccine in a standard 3+3 design.

Intervention Type: BIOLOGICAL

Phase II - GM.CD40L cells Vaccinations

Patients randomized to Arm A will receive vaccinations on 3 occasions, at 2 week intervals. 7.5 X 10\^6 irradiated H1944 tumor cells, 7.5 X 10\^6 irradiated H2122 cells, and containing 15 X 10\^6 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.

Intervention Type: BIOLOGICAL

Phase II - GM.CD40L.CCL21 Vaccinations

This is a dual-agent, Phase I study with an expansion of each group at the recommended Phase II dose. Participants are entered in cohorts of 3 at the first dose level. Doses are not escalated over the course of treatment of an individual patient.

Phase II: Participants are randomized to one of the 2 arms (ratio 1:1): GM.CD40L versus GM.CD40L.CCL21. 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.

Intervention Type: BIOLOGICAL

Other Intervention Names

chemokine; MHC-negative cell line; chemokine

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bankhead-Coley Florida Biomedical Research Program

UNKNOWN

Sponsor Role: collaborator

James and Esther King Biomedical Research Program

OTHER

Sponsor Role: collaborator

H. Lee Moffitt Cancer Center and Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jhanelle Gray, M.D.

Role: PRINCIPAL_INVESTIGATOR

H. Lee Moffitt Cancer Center and Research Institute

Locations

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Countries

United States

Other Identifiers

MCC-16439

Identifier Type: -

Identifier Source: org_study_id