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

Primary Purpose

Lung Cancer, Adenocarcinoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Phase I - GM.CD40L.CCL21 Vaccinations
Phase II - GM.CD40L cells Vaccinations
Phase II - GM.CD40L.CCL21 Vaccinations
Sponsored by
H. Lee Moffitt Cancer Center and Research Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lung Cancer focused on measuring 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)

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • H. Lee Moffitt Cancer Center and Research Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

Phase I Vaccinations

Phase II Arm A Vaccinations

Phase II Arm B Vaccinations

Arm Description

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.

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.

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.

Outcomes

Primary Outcome Measures

Phase I: Recommend Phase II Dose (RPDII)
Highest dose level of GMCD40L vaccine in combination with CCL21 that induced dose limiting toxicity (DLT) in fewer than 33% of patients. DLT: Intervention-specific acute toxicity; i.e., occurrence within 28 days of drug administration, according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), V 4: 1.) that precludes further dose escalation. 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. If 2 or more patients experience toxicity in dose level 1 (30X10^6 cells per injection), dose de-escalation will occur. Dose level -1 will be defined by 10 % reduction of cells administered from dose level 1 and follow the same rules. It is not feasible to escalate the dose of the vaccine beyond 30X10^6 cells per injection; therefore the Maximum Tolerated Dose (MTD) may not be reached in this study. In that case, the highest dose level will be used in the phase II component.
Phase II: Progression Free Survival (PFS)
PFS is measured as the time from start of treatment to progression or death. 6 month progression free survival will be estimated from available clinical and radiographic assessments and RECIST 1.1 will be used to make tumor measurements. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions.

Secondary Outcome Measures

Response Rate
Response according to Response Evaluation in Solid Tumors (RECIST) 1.1. Complete Response (CR): Complete disappearance of all measurable and non-measurable disease; No new lesions. Partial Response (PR): Applies only to patients with at least one measurable lesion; Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. Progressive Disease (PD): 20% or greater increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Stable Disease (SD): Does not qualify for CR, PR, Progression or Symptomatic Deterioration; All target measurable lesions must be assessed using the same techniques as baseline.

Full Information

First Posted
September 12, 2011
Last Updated
August 5, 2019
Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Bankhead-Coley Florida Biomedical Research Program, James and Esther King Biomedical Research Program
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1. Study Identification

Unique Protocol Identification Number
NCT01433172
Brief Title
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

2. Study Status

Record Verification Date
August 2019
Overall Recruitment Status
Completed
Study Start Date
March 26, 2012 (Actual)
Primary Completion Date
January 31, 2016 (Actual)
Study Completion Date
February 1, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
H. Lee Moffitt Cancer Center and Research Institute
Collaborators
Bankhead-Coley Florida Biomedical Research Program, James and Esther King Biomedical Research Program

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
73 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Phase I Vaccinations
Arm Type
Experimental
Arm Description
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.
Arm Title
Phase II Arm A Vaccinations
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Phase II Arm B Vaccinations
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Phase I - GM.CD40L.CCL21 Vaccinations
Other Intervention Name(s)
chemokine
Intervention Description
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
Intervention Name(s)
Phase II - GM.CD40L cells Vaccinations
Other Intervention Name(s)
MHC-negative cell line
Intervention Description
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
Intervention Name(s)
Phase II - GM.CD40L.CCL21 Vaccinations
Other Intervention Name(s)
chemokine
Intervention Description
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.
Primary Outcome Measure Information:
Title
Phase I: Recommend Phase II Dose (RPDII)
Description
Highest dose level of GMCD40L vaccine in combination with CCL21 that induced dose limiting toxicity (DLT) in fewer than 33% of patients. DLT: Intervention-specific acute toxicity; i.e., occurrence within 28 days of drug administration, according to the NCI Common Toxicity Criteria for Adverse Events (CTCAE), V 4: 1.) that precludes further dose escalation. 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. If 2 or more patients experience toxicity in dose level 1 (30X10^6 cells per injection), dose de-escalation will occur. Dose level -1 will be defined by 10 % reduction of cells administered from dose level 1 and follow the same rules. It is not feasible to escalate the dose of the vaccine beyond 30X10^6 cells per injection; therefore the Maximum Tolerated Dose (MTD) may not be reached in this study. In that case, the highest dose level will be used in the phase II component.
Time Frame
Up to 6 Months
Title
Phase II: Progression Free Survival (PFS)
Description
PFS is measured as the time from start of treatment to progression or death. 6 month progression free survival will be estimated from available clinical and radiographic assessments and RECIST 1.1 will be used to make tumor measurements. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions.
Time Frame
Up to 6 Months
Secondary Outcome Measure Information:
Title
Response Rate
Description
Response according to Response Evaluation in Solid Tumors (RECIST) 1.1. Complete Response (CR): Complete disappearance of all measurable and non-measurable disease; No new lesions. Partial Response (PR): Applies only to patients with at least one measurable lesion; Greater than or equal to 30% decrease under baseline of the sum of longest diameters of all target measurable lesions. Progressive Disease (PD): 20% or greater increase in the sum of longest diameters of target measurable lesions over smallest sum observed (over baseline if no decrease during therapy) using the same techniques as baseline. Unequivocal progression of non-measurable disease in the opinion of the treating physician (an explanation must be provided). Appearance of any new lesion/site. Stable Disease (SD): Does not qualify for CR, PR, Progression or Symptomatic Deterioration; All target measurable lesions must be assessed using the same techniques as baseline.
Time Frame
Up to 12 Months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jhanelle Gray, M.D.
Organizational Affiliation
H. Lee Moffitt Cancer Center and Research Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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