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

NCT01433172 | Completed Phase 1 Results DMC

• 1 other identifier: MCC-16439
• Study Type: interventional
• Target: 73
• Locations: 1 country
• Sites: 1

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.

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)

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 6 Months

• 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.

  Up to 6 Months

Secondary Outcomes (1)

• Response Rate

  Up to 12 Months

Study Arms (3)

Phase I Vaccinations

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.

Biological: Phase I - GM.CD40L.CCL21 Vaccinations

Phase II Arm A Vaccinations

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.

Biological: Phase II - GM.CD40L cells Vaccinations

Phase II Arm B Vaccinations

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.

Biological: Phase II - GM.CD40L.CCL21 Vaccinations

Interventions

Phase I - GM.CD40L.CCL21 Vaccinations 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.

Also known as: chemokine

Phase I Vaccinations

Phase II - GM.CD40L cells Vaccinations 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.

Also known as: MHC-negative cell line

Phase II Arm A Vaccinations

Phase II - GM.CD40L.CCL21 Vaccinations 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.

Also known as: chemokine

Phase II Arm B Vaccinations

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• H. Lee Moffitt Cancer Center and Research Institute: lead
• Bankhead-Coley Florida Biomedical Research Program: collaborator
• James and Esther King Biomedical Research Program: collaborator

Study Sites (1)

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

MeSH Terms

Conditions

Lung Neoplasms; Adenocarcinoma

Interventions

Chemokines

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Chemotactic Factors; Biological Factors; Inflammation Mediators

Results Point of Contact

• Title: Dr. Jhanelle Gray
• Organization: H. Lee Moffitt Cancer Center and Research Institute

jhanelle.gray@moffitt.org

813-745-3050

Study Officials

• Jhanelle Gray, M.D.

  H. Lee Moffitt Cancer Center and Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2011
• First Posted: September 13, 2011
• Study Start: March 26, 2012
• Primary Completion: January 31, 2016
• Study Completion: February 1, 2019
• Last Updated: August 6, 2019
• Results First Posted: April 5, 2017

Record last verified: 2019-08

Locations

US (1)