Cyclophosphamide, TAPA-Pulsed Dendritic Cell Therapy and Imiquimod in Progressive and/or Refractory Solid Malignancies

NCT02224599 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: KIROVAX-003
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Patients diagnosed with progressive and/or refractory solid malignancies, who have failed conventional therapy, and have no available, potentially curative therapeutic options, will be candidates for this Phase I/II study. Following confirmation of disease progression and/or refractoriness, eligible patients who agree to participate and sign an informed consent form will have their tumor cells/tissues and/or blood analyzed for the expression of a specific panel of Tumor Associated Peptide Antigens (TAPAs), including Sp17, ropporin, AKAP-4, PTTG1, Span-xb, Her-2/neu, HM1.24, NY-ESO-1 and MAGE-1.

Conditions

Progressive Solid Malignancies; Refractory Solid Malignancies; Cancer

Keywords

Immunotherapy; TAPA-Pulsed Dendritic Cell Therapy; Dendritic Cell Therapy

Outcome Measures

Primary Outcomes (1)

• Adverse Events Due to Administration of TAPA-Pulse DC Vaccine

  Grade, causality, start/stop dates (duration), resolutions for adverse events will be monitored and recorded.

  Continuous for 45 days after the first dose.

Secondary Outcomes (2)

• Immune Response

  Days -7, 22 and 45

• Positive DTH Skin Tests With Relevant TAPA

  Days -7, 22 and 45

Study Arms (1)

CYP, TAPA-pulsed DC vaccine, Imiquimod

EXPERIMENTAL

TAPA-Pulsed DC Vaccine Cyclophosphamide Pill Imiquimod Topical Cream

Biological: TAPA-pulsed DC vaccine; Drug: Cyclophosphamide Pill; Drug: Imiquimod Topical Cream

Interventions

TAPA-pulsed DC vaccine BIOLOGICAL

Subjects will given the vaccine which contains 1 x 10\^7 TAPA-pulsed dendritic cells and is administered ID. A total of three (3) cycles therapy will be administered weekly.

CYP, TAPA-pulsed DC vaccine, Imiquimod

Cyclophosphamide Pill DRUG

Subjects will be given low-dose cyclophosphamide by mouth for 5 days starting 5 to 7 days prior to the vaccine cycle.

Also known as: Cytoxan®, Neosar®

CYP, TAPA-pulsed DC vaccine, Imiquimod

Imiquimod Topical Cream DRUG

Topical Imiquimod Cream will be applied after vaccination.

Also known as: Aldara Cream, Zyclara

CYP, TAPA-pulsed DC vaccine, Imiquimod

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent.
• Patients with histologically proven progressive and/or refractory SM, s/p conventional salvage therapy, completed at least 3 weeks prior to study vaccination, will be eligible for enrollment.
• 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 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.
• Presence of measurable or evaluable disease.
• Patients must not have any active infectious process.
• Patients must not have a history of HIV, or active Hepatitis A, B, and C.
• Patients must not be receiving active immunosuppressive therapy.
• Patients must have discontinued systemic cytotoxic or radiation therapy at least three (3) weeks prior to vaccination and toxicities from previous therapies must be grade 1 or less. all other FDA approved forms of antineoplastic therapy are allowed such as immunotherapy, targeted therapies, or hormonal therapies (67, 68)
• Patients may not have any known allergy to CYP and/or Imiquimod.
• Patients must be willing to provide at least 250 mL, and up to 500 mL, 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, AST and ALT ≤ 4X upper limit of normal range).
• Adequate hematologic function (Platelets ≥ 60,000/mm3, lymphocytes ≥ 1,000 mm3, neutrophils ≥ 750/mm3, hemoglobin ≥ 9.0 g/dl).
• Karnofsky performance status ≥ 70%.
• Expected survival ≥ 6 months.
• Either a female or male of reproductive capacity wishing to participate in this study must be using, or agree to use, one or more types of birth control during the entire study and for 3 months after completing the study. Birth control methods may include condoms, diaphragms, birth control pills, spermicidal gels or foams, anti-gonadotropin injections, intrauterine devices (IUD), surgical sterilization, or subcutaneous implants. Another choice is for a subject's sexual partner to use one of these birth control methods. Women of reproductive capacity will be required to undergo a urine pregnancy test before completion of the post-screening informed consent process.

You may not qualify if:

• Patients without confirmed progressive and/or refractory SM using standard RECIST criteria.
• Patients without measurable or evaluable disease.
• Patients receiving cytotoxic therapy or radiation therapy, within three (3) weeks of vaccination.
• Active immunosuppressive therapy, including non-physiologic systemic steroids (excluding topical, intraocular, inhaled, and intranasal 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), Inflammatory Bowel Disease (IBD) and Rheumatoid Arthritis (RA).
• Pregnancy or breast feeding.
• Active second invasive malignancy, other than basal cell carcinoma of the skin.
• Life expectancy of less than 6 months.
• Patients with contraindications to CYP and/or Imiquimod.
• Patients who have received organ transplants.
• Patients with psychological or geographic conditions that prevent adequate follow- up or compliance with the study protocol.

Sponsors & Collaborators

• Kiromic BioPharma Inc.: lead

Study Sites (1)

Unknown Facility

San Antonio, Texas, 78240, United States

Location

MeSH Terms

Conditions

Neoplasms

Interventions

Cyclophosphamide; Imiquimod

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: CMO and Head of Clinical Operations
• Organization: Kiromic

sdahlbeck@kiromic.com

(832) 968-4888

Study Officials

• Anthony Tolcher, MD

  NEXT Oncology

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

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: August 11, 2014
• First Posted: August 25, 2014
• Study Start: July 28, 2017
• Primary Completion: August 30, 2018
• Study Completion: August 30, 2018
• Last Updated: April 24, 2020
• Results First Posted: April 24, 2020

Record last verified: 2020-03

Locations

US (1)