Consolidation Therapy in Patients With Metastatic Solid Malignancies

NCT02705703 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: KiroVAX004BSK01 Dendritic cell vaccine
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study evaluates the effectiveness of Tumor Associated Peptide Antigens (TAPA) pulsed dendritic cell injections as a potential consolidation therapy for patients with metastatic solid malignancies (SM). The investigators hypothesize that treatment of patients with metastatic SM who demonstrate a tumor response, or whose disease remains stable, after conventional first-line systemic therapy AND who lack an available, potentially curative therapeutic intervention and whose tumor cells and/or blood express at least one (1) TAPA of a defined panel of TAPAs will result in TAPA-specific T-cell responses without significant toxicities. The investigators also hypothesize CD4+ and CD8+ T-cell responses generated against specific TAPAs may translate into clinical antitumor activity.

Conditions

Cancer; Metastatic Solid Malignancies

Outcome Measures

Primary Outcomes (1)

• Number of adverse events due to administration of TAPA-pulse DC vaccine

  every 7 days up to 5 months

Secondary Outcomes (2)

• Immunological efficacy as indicated by T-cell cytokine levels

  up to 5 months

• Immunological efficacy as determined by a positive delayed type hypersensitivity (DTH) skin test

  up to 5 months

Study Arms (1)

TAPA-pulsed DC vaccine

EXPERIMENTAL

The subject will take low-dose cyclophosphamide by mouth for 5 days starting 7 days prior to the vaccine cycle. The vaccine contains 1 x 10\^7 TAPA-pulsed dendritic cells and is administered SQ with low-dose GM-CSF following the low-dose cyclophosphamide cycle. A total of six (6) cycles of cyclophosphamide and six (6) DC vaccines cycles will be administered alternating every 14 days.

Biological: TAPA-pulsed DC vaccine

Interventions

TAPA-pulsed DC vaccine BIOLOGICAL

A cycle of low-dose cyclophosphamide (100mg/day) by mouth for 5 days starting seven 7 days prior to the DC vaccine cycle to reduce Treg activity. Low-dose cyclophosphamide will be taken every 14 days for six 6 cycles. A total of 6 vaccines containing 1 x 10\^7 TAPA-pulsed DC will be administered SQ every 14 days. The DC vaccine is given on Day 1 of the DCV cycle plus low-dose GM-CSF 50mcg/day SQ x 5 days (Day 1 to Day 4). GM-CSF is administered for 5 days to increase monocyte production and dendritic cell precursors to optimize immune responses.

TAPA-pulsed DC vaccine

Eligibility Criteria

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

You may qualify if:

• Ability to provide informed consent.
• Patients at least eighteen (18) years of age with histologically proven metastatic solid malignancies (SM) AND whose SM demonstrates a response, or whose disease remains stable, after conventional, first-line systemic therapy, AND who lack any available, potentially curative therapeutic intervention, will be eligible for participation in this study.
• Expression of one (1) or more of the following TAPAs; Sp17, AKAP-4, Ropporin, PTTG-1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1, by either reverse transcriptase polymerase chain reaction (RT-PCR) and/or immunocytochemistry, Western blotting or ELISA, in neoplastic cells and/or blood. For HER-2/neu expression, positive FISH results are acceptable. All lab tests will be performed in a CLIA certified facility
• Presence of measurable or evaluable disease.
• Patients must not have any active infectious process.
• Patients must have a negative test for HIV, Hepatitis A, B, and C.
• Patients must not be receiving active immunosuppressive therapy.
• Patients must have discontinued systemic antineoplastic therapy (including endocrine and biological agents, as well as systemic corticosteroids) at least three (3) to four (4) weeks prior to enrollment. Toxicities from previous therapies must be grade 1 or less.
• Patients may not have any known allergy to GM-CSF.
• Patients must be willing to provide at least 250 mls of whole blood obtained by phlebotomy and/or consent to leukapheresis for DC generation.
• Adequate renal and hepatic function (creatinine ≤ 2.0 mg/dl, bilirubin ≤ 2.0 mg/dl, aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 4X upper limit of normal range).
• Adequate hematologic function (Platelets ≥ 60,000/mm3, lymphocytes ≥ 1,000 mm3, neutrophils ≥ 750/mm3, hemoglobin ≥ 10.0 g/dl).
• Karnofsky performance status ≥ 70%.
• Expected survival ≥ 6 months.
• Patient Human Leucocyte Antigen (HLA) typing should demonstrate HLA-A\*01, and/or HLA-A\*02, and/or HLA-A\*24 subtype restriction.

You may not qualify if:

• Patients without confirmed metastatic SM and/or response to conventional, first-line systemic therapy using standard RECIST criteria, or patients with confirmed metastatic SM and/or response to conventional, first-line systemic therapy using standard RECIST criteria, but who have an available, potentially curative therapeutic option will be excluded from participation in this study.
• Patients without measurable or evaluable disease.
• Patients receiving cytotoxic therapy (including endocrine and biological agents), radiation therapy, immunotherapy or non-topical steroids, within three (3) weeks of enrollment.
• Active immunosuppressive therapy (excluding topical steroids) for any other condition.
• Persistent fever (\>24 hours) documented by repeated measurement or active, uncontrolled infection within 4 weeks of enrollment.
• Active ischemic heart disease or history of myocardial infarction within six months.
• Active autoimmune disease, including, but not limited to, Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS), Ankylosing Spondylitis (AS), and Rheumatoid Arthritis (RA).
• Pregnancy or breast feeding.
• Active second invasive malignancy, other than basal cell carcinoma of the skin.
• Life expectancy ≤ 6 months.
• Patients with contraindications to CYP and/or GM-CSF.
• History of allergy to CYP and/or GM-CSF.
• Patients who have received organ transplants.
• Patients with psychological or geographic conditions that prevent adequate follow-up or compliance with the study protocol.
• Patients diagnosed with central nervous system (CNS) metastases or involvement at any time during disease course are excluded from the study.

Sponsors & Collaborators

• Kiromic BioPharma Inc.: lead

MeSH Terms

Conditions

Neoplasms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2016
• First Posted: March 10, 2016
• Study Start: July 28, 2017
• Primary Completion: October 31, 2018
• Study Completion: January 31, 2019
• Last Updated: August 28, 2018

Record last verified: 2018-01