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

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by H. Lee Moffitt Cancer Center and Research Institute
Sponsor:
Collaborators:
Bankhead-Coley Florida Biomedical Research Program
James and Esther King Biomedical Research Program
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT01433172
First received: September 12, 2011
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Lung Cancer
Adenocarcinoma
Biological: GM.CD40L.CCL21 Vaccinations
Biological: GM.CD40L cells Vaccinations
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by H. Lee Moffitt Cancer Center and Research Institute:

Primary Outcome Measures:
  • Number of Participants With Progressive Free Survival (PFS) [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    Once the maximum tolerated dose (MTD) is established in the phase I, additional patients will be enrolled at this dose level to a total of 64 on a randomized phase II trial (32 per each arm). The primary endpoint for the trial will be 6-month progression free survival (PFS).


Secondary Outcome Measures:
  • Number of Participants With Adverse Events [ Time Frame: Average of 12 Months ] [ Designated as safety issue: Yes ]
    The toxicity safety endpoint (Grade ≥ 2 immunologic toxicity (except fever), grade ≥ 3 non-hematologic or grade ≥ 4 hematologic adverse event) will be monitored continuously through the trial.


Estimated Enrollment: 76
Study Start Date: March 2012
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: GM.CD40L.CCL21 Vaccinations

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.

Other Name: chemokine
Active Comparator: 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.
Biological: GM.CD40L cells Vaccinations
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.
Other Name: MHC-negative cell line
Active Comparator: 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.
Biological: GM.CD40L.CCL21 Vaccinations

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.

Other Name: chemokine

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01433172

Contacts
Contact: Jhanelle Gray, M.D. 813-745-7282 jhanelle.gray@moffitt.org

Locations
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute Recruiting
Tampa, Florida, United States, 33612
Contact: Germaine Gonzalez-Vazquez    813-745-8350    germaine.gonzalez-vazquez@moffitt.org   
Principal Investigator: Jhanelle Gray, M.D.         
Sub-Investigator: Scott Antonia, M.D., Ph.D.         
Sub-Investigator: Alberto Chiappori, M.D.         
Sub-Investigator: Eric Haura, M.D.         
Sub-Investigator: Martine Extermann, M.D., Ph.D.         
Sub-Investigator: Tawee Tanvetyanon, M.D.         
Sub-Investigator: Charles Williams, M.D.         
Sub-Investigator: Soner Altiok, M.D.         
Sponsors and Collaborators
H. Lee Moffitt Cancer Center and Research Institute
Bankhead-Coley Florida Biomedical Research Program
James and Esther King Biomedical Research Program
Investigators
Principal Investigator: Jhanelle Gray, M.D. H. Lee Moffitt Cancer Center and Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier: NCT01433172     History of Changes
Other Study ID Numbers: MCC-16439
Study First Received: September 12, 2011
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by H. Lee Moffitt Cancer Center and Research Institute:
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)

Additional relevant MeSH terms:
Adenocarcinoma
Lung Neoplasms
Carcinoma
Lung Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms

ClinicalTrials.gov processed this record on October 23, 2014