CancerPhase 1/2NCT02705703
Consolidation Therapy in Patients With Metastatic Solid Malignancies
A Phase 1/2 study testing TAPA-pulsed DC vaccine in people with Cancer and Metastatic Solid Malignancies, run by Kiromic BioPharma Inc..
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cancer, Metastatic Solid Malignancies
- What is being tested?
- TAPA-pulsed DC vaccine
- Type of treatment
- Vaccines, Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- 28 Jul 2017to 31 Jan 2019
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
- 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.
Who cannot join
- 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.
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- 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.
- Patient with HLA alleles not belonging to any of the following subtypes: HLA-A*01, or HLA-A*02, or HLA-A*24.
About this study
Official title: Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen (TAPA)-Pulsed Dendritic Cell (DC) Therapy and Low Dose GM-CSF, as Consolidation Therapy in Patients With Metastatic Solid Malignancies
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.
Read the detailed description
Patients diagnosed with metastatic solid malignancies (SM), who have responded or whose disease remains stable following first line systemic therapy, and without available, potential curative therapeutic options, will be candidates for this Phase I/II study. Potentially eligible patients who agree to participate and sign a consent form will have their neoplastic cells 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. 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 for generation of autologous DCs. Patient's DCs will be generated in Kiromic's Cell Processing Good Manufacturing Process (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 responses 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/or immune responses (Phase II).
- Conditions
- Cancer, Metastatic Solid Malignancies
- Being tested
- TAPA-pulsed DC vaccine
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TAPA-pulsed DC vaccineBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Biological: TAPA-pulsed DC vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of adverse events due to administration of TAPA-pulse DC vaccine
Measured: every 7 days up to 5 months
Secondary outcomes (2)
Immunological efficacy as indicated by T-cell cytokine levels
Measured: up to 5 months
Immunological efficacy as determined by a positive delayed type hypersensitivity (DTH) skin test
Measured: up to 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Mar 2016 (estimated)
- Study start28 Jul 2017
- Primary completion31 Oct 2018 (estimated)
- Study completion31 Jan 2019 (estimated)
Why it stopped: Sponsor decision to discontinue study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Kiromic BioPharma Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02705703
- Sponsor's protocol ID
- KiroVAX004
- Other IDs
- BSK01 Dendritic cell vaccine
- Status last verified
- Jan 2018
- First submitted
- 7 Mar 2016
- Last updated
- 28 Aug 2018
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Low-Dose Cyclophosphamide, Tumor Associated Peptide Antigen (TAPA)-Pulsed Dendritic Cell (DC) Therapy and Low Dose GM-CSF, as Consolidation Therapy in Patients With Metastatic Solid Malignancies
- ClinicalTrials.gov ID
- NCT02705703
- Acronym / sponsor ID
- KiroVAX004
- Conditions
- Cancer, Metastatic Solid Malignancies
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Sponsor decision to discontinue study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Kiromic BioPharma Inc.Industry (pharma, biotech, devices)
- Study start
- 28 Jul 2017 (actual)
- Primary completion
- 31 Oct 2018 (estimated)
- Study completion
- 31 Jan 2019 (estimated)
- First posted
- 10 Mar 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients diagnosed with metastatic solid malignancies (SM), who have responded or whose disease remains stable following first line systemic therapy, and without available, potential curative therapeutic options, will be candidates for this Phase I/II study. Potentially eligible patients who agree to participate and sign a consent form will have their neoplastic cells 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. 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 for generation of autologous DCs. Patient's DCs will be generated in Kiromic's Cell Processing Good Manufacturing Process (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 responses 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/or immune responses (Phase II).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TAPA-pulsed DC vaccine | Experimental | Biological: TAPA-pulsed DC vaccineThe 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TAPA-pulsed DC vaccineA 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. | Biological | TAPA-pulsed DC vaccine |
Primary outcome
Number of adverse events due to administration of TAPA-pulse DC vaccine
Time frame: every 7 days up to 5 months
2 secondary outcomes
Immunological efficacy as indicated by T-cell cytokine levels
Time frame: up to 5 months
Immunological efficacy as determined by a positive delayed type hypersensitivity (DTH) skin test
Time frame: up to 5 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Aug 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing TAPA-pulsed DC vaccine in people with Cancer and Metastatic Solid Malignancies, run by Kiromic BioPharma Inc..
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 28 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of adverse events due to administration of TAPA-pulse DC vaccine (time frame: every 7 days up to 5 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Aug 2018.