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Trial record 3 of 4 for:    kiromic

Treatment of Patients With Progressive and/or Refractory Solid Malignancies

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ClinicalTrials.gov Identifier: NCT02224599
Recruitment Status : Recruiting
First Posted : August 25, 2014
Last Update Posted : June 11, 2018
Sponsor:
Information provided by (Responsible Party):
Kiromic, Inc.

Brief Summary:
Patients diagnosed with progressive and/or refractory solid malignancies (SM), 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 a 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.

Condition or disease Intervention/treatment Phase
Progressive Solid Malignancies Refractory Solid Malignancies Cancer Biological: TAPA-pulsed DC vaccine Phase 1 Phase 2

Detailed Description:
Patients whose tumors express one (1) or more of these TAPAs will receive three (3) days of subcutaneous Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) to increase bone marrow production of monocytes and dendritic cell (DC) precursors, and whole blood will be obtained by phlebotomy and/or leukapheresis performed for generation of autologous DCs. Patient's DCs will be generated in Kiromic's Cell Processing GMP facility, according to established Standard Operating Procedures, and activated by pulsing/loading them with the TAPA(s) relevant for each particular patient. Patients will receive five (5) days of low-dose cyclophosphamide prior to each vaccination with TAPA-pulsed DCs to decrease Treg activity. TAPA-pulsed DCs will be administered at a fixed dose of up to 1 X 107 DCs at least two (2) days following cyclophosphamide administration. DC vaccination schedule will be once every fourteen (14) days via subcutaneous (SC) and intradermal (ID) injections for a total of 6 vaccinations. Low dose GM-CSF will also be administered SC for five (5) consecutive days, starting three (3) to six (6) hours after each TAPA-pulsed DC treatment, to optimize immune responses. Patients will be followed on a weekly basis (or more frequently if required) to evaluate treatment-related toxicity. Immune efficacy and anti-tumor responses will be evaluated per protocol specifications. Continuation and stopping rules for the study will be defined based on toxicity/tolerability (Phase I) and immune efficacy (Phase II).

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 23 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen-Pulsed Dendritic Cell Therapy and Low Dose Granulocyte-Macrophage Colony Stimulating Factor, in Patients With Progressive and/or Refractory Solid Malignancies
Actual Study Start Date : July 28, 2017
Estimated Primary Completion Date : October 31, 2018
Estimated Study Completion Date : January 31, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: TAPA-pulsed DC vaccine
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 ID 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
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 ID 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.




Primary Outcome Measures :
  1. Number of adverse events due to administration of TAPA-pulse DC vaccine [ Time Frame: Every 7 days up to 5 months ]

Secondary Outcome Measures :
  1. Immunological efficacy as indicated by T-cell cytokine levels [ Time Frame: up to 5 months ]
    First evaluation will be 8-10 days before first DC vaccine. Additional evaluations on days 14, 28, 42, 56, and 70 of trial as well as 14 and 60 days after the last vaccine administered.

  2. Immunological efficacy as determined by a positive delayed type hypersensitivity (DTH) skin test [ Time Frame: up to 5 months ]
    DTH skin test will be performed 8-10 days before vaccine administration. DTH response will be evaluated again at days 28 and 70 of the trial as well as 14 and 60 days after the trial has ended



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Ability to provide informed consent.
  2. Patients at least eighteen (18) years of age with histologically proven, progressive and/or refractory SM.
  3. 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.
  4. Presence of measurable or evaluable disease.
  5. Patients must not have any active infectious process.
  6. Patients must not have a history of HIV, or active Hepatitis A, B, and C.
  7. Patients must not be receiving active immunosuppressive therapy.
  8. 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.
  9. Patients may not have any known allergy to CYP and/or GM-CSF.
  10. 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.
  11. Adequate renal and hepatic function (creatinine ≤ 2.0 mg/dl, bilirubin ≤ 2.0 mg/dl, AST and ALT ≤ 4X upper limit of normal range).
  12. Adequate hematologic function (Platelets ≥ 60,000/mm3, lymphocytes ≥ 1,000 mm3, neutrophils ≥ 750/mm3, hemoglobin ≥ 9.0 g/dl).
  13. Karnofsky performance status ≥ 70%.
  14. Expected survival ≥ 6 months.
  15. 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.
  16. Patient Human Leucocyte Antigen (HLA) typing should demonstrate HLA-A*01, and/or HLA-A*02, and/or HLA-A*24 restriction.

Exclusion Criteria:

  1. Patients without confirmed progressive and/or refractory SM using standard RECIST criteria, or those with confirmed progressive and/or refractory SM using standard RECIST criteria.
  2. Patients without measurable or evaluable disease.
  3. Patients receiving cytotoxic therapy (including endocrine and biological agents), radiation therapy, immunotherapy or non-topical steroids, within three (3) to four (4) weeks of enrollment.
  4. Active immunosuppressive therapy (excluding topical steroids) for any other condition.
  5. Persistent fever (>24 hours) documented by repeated measurement or active, uncontrolled infection within 4 weeks of enrollment.
  6. Active ischemic heart disease or history of myocardial infarction within six months.
  7. Active autoimmune disease, including, but not limited to, Systemic Lupus Erythematosus (SLE), Multiple Sclerosis (MS), Ankylosing Spondylitis (AS), and Rheumatoid Arthritis (RA).
  8. Pregnancy or breast feeding.
  9. Active second invasive malignancy, other than basal cell carcinoma of the skin.
  10. Life expectancy of less than 6 months.
  11. Patients with contraindications to CYP and/or GM-CSF.
  12. Patients who have received organ transplants.
  13. Patients with psychological or geographic conditions that prevent adequate follow- up or compliance with the study protocol.
  14. Patients diagnosed with primary central nervous system (CNS) or with CNS metastases or involvement, at any time during the disease course, are excluded from the study.
  15. Patients without HLA-A1, or HLA-A*02, or HLA-A*24 restriction.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02224599


Contacts
Contact: Diane D Nguyen, DO 806-787-4374 dnguyen@kiromic.com
Contact: Scott Dahlbeck, MD, PharmD 713-689-4450 sdahlbeck@kiromic.com

Locations
United States, Texas
The Urology Place Recruiting
San Antonio, Texas, United States, 78240
Contact: Melissa Scott    210-617-3670    melissa.scott@theupi.com   
Contact: Naveen Kella, MD    210-617-3670      
Sponsors and Collaborators
Kiromic, Inc.
Investigators
Principal Investigator: Naveen Kella, MD The Urology Place

Responsible Party: Kiromic, Inc.
ClinicalTrials.gov Identifier: NCT02224599     History of Changes
Other Study ID Numbers: Kirovax 003
BSK01 Dendritic cell vaccine ( Other Identifier: Kiromic )
First Posted: August 25, 2014    Key Record Dates
Last Update Posted: June 11, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Neoplasms
Vaccines
Cyclophosphamide
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists