Leukemia, Lymphocytic, Chronic, B-CellPhase 2NCT03265717
DNA Plasmid Encoding a Modified Human Telomerase Reverse Transcriptase (hTERT), Invac-1 in Chronic Lymphocytic Leukemia
A Phase 2 study testing INVAC-1 in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Invectys at 1 site in United States.
Trial summary
Phase 2 study to assess the efficacy of INVAC-1, a DNA plasmid encoding a modified human telomerase reverse transcriptas (hTERT) protein, at a dose of 800 µg for 6 cycles 4 weeks apart on Minimal Residual Disease (MRD) eradication rate in the bone marrow, either as a single agent in a high risk "watch and wait" group… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Lymphocytic, Chronic, B-Cell
- What is being tested?
- INVAC-1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Jul 2018to 30 Jun 2020
- Phase
- Phase 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
- Age ≥ 18 years old
- Rai stage 0 - II without active disease according to IWCLL 2018 criteria
- Predicted time to first treatment of ≤3 years according to MDACC nomogram.
- ECOG performance status of 0-2
- Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 1.5 x ULN except Gilbert's Syndrome where a direct bilirubin ≤ 1.5 ULN will be used.
- Adequate renal function, defined as an estimated creatinine clearance ≥30 mL/min using the Cockcroft-Gault equation
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- Willingness to receive all outpatient treatment, all laboratory monitoring, and all radiological evaluations at the institution that administers study drug for the entire study
- Willingness of male and female patients, if sexually active, to use an effective barrier method of contraception during the study and for 3 months following the last dose of study drug
- Ability to provide written informed consent and to understand and comply with the requirements of the study
- Age ≥ 18 years old
- Males or females with CLL diagnosed according to IWCLL diagnostic criteria who have been treated with ibrutinib therapy for at least 12 months and have had no more than 1 other treatment for CLL prior to receiving ibrutinib.
- Currently in complete or partial remission (PR)/PR with lymphocytosis (PRL)
- MRD positivity defined as >0.5% CLL cells in the bone marrow by flow cytometry
- ECOG performance status of 0-2
- Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 1.5 x ULN, unless Gilbert's Syndrome where a direct bilirubin ≤ 1.5 ULN will be used.
- Adequate renal function, defined as estimated creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault equation
- Willingness to receive all outpatient treatment, all laboratory monitoring, and all radiological evaluations at the institution that administers study drug for the entire study
- Willingness of male and female patients, if sexually active, to use an effective barrier method of contraception during the study and for 3 months following the last dose of study drug
- Ability to provide written informed consent and to understand and comply with the requirements of the study
Who cannot join
- Any investigational agent(s) within 4 weeks prior to entry
- Uncontrolled autoimmune hemolytic anemia (Hgb < 11g/deciliter) or idiopathic thrombocytopenic purpura (< 100,000/µl)
- Any previous treatment (chemotherapy, radiotherapy, and/or monoclonal antibodies) intended specifically to treat CLL
- Treatment with corticosteroids other than physiological replacement within the previous week or treatment with immunosuppressive medication within the previous week.
- Major surgery within 4 weeks prior to inclusion
- Currently active, clinically significant cardiovascular disease or a history of myocardial infarction within 6 months prior to inclusion
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- Uncontrolled active systemic fungal, bacterial, viral, or other infection or requirement for intravenous (IV) antibiotics
- Known history of infection with human immunodeficiency virus (HIV)
- Serologic status reflecting active hepatitis B or C infection.
- History of stroke or intracranial hemorrhage within 6 months prior to enrolment
- Current life-threatening illness, medical condition, or organ-system dysfunction that could compromise patient safety or put the study at risk
- Breast-feeding or pregnant women, or patients for whom there is a risk of conception and who are unable or unwilling to use appropriate contraception (for male and female patients up to 4 months after end of ibrutinib.)
- Previous malignancy with life expectancy less than 6 months or requiring systemic treatment (except colorectal cancer, history of basal cell carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment)
- Known drug abuse/ alcohol abuse
- Severe organ failures or diseases, including: clinically relevant coronary disease, myocardial infarction or any other relevant cardiovascular disorder within 12 months before study entry, severe psychiatric illness and severe infection.
- Group 2: Ibrutinib treated patients
- Any investigational agent(s) within 4 weeks prior to entry
- Known involvement of the central nervous system by lymphoma or leukemia
- History or current evidence of Richter's transformation or prolymphocytic leukemia
- Uncontrolled autoimmune hemolytic anemia (Hgb < 11g/deciliter) or idiopathic thrombocytopenic purpura (< 100,000/µl)
- More than one previous treatment by chemotherapy or patients who previously received alemtuzumab intended specifically to treat CLL
- Corticosteroid use within 1 week prior to first dose of study drug, with the exception of inhaled, topical, or other local administrations. Patients requiring systemic steroids at daily doses > 20 mg prednisone (or corticosteroid equivalent), or those who are administered steroids for leukemia control or white blood cell (WBC)-count-lowering are excluded
- Major surgery within 4 weeks prior to inclusion
- Currently active, clinically significant cardiovascular disease or a history of myocardial infarction within 6 months prior to inclusion
- Uncontrolled active systemic fungal, bacterial, viral, or other infection or requirement for intravenous (IV) antibiotics
- Known history of infection with human immunodeficiency virus (HIV)
- Serologic status reflecting active hepatitis B or C infection
- History of stroke or intracranial hemorrhage within 6 months prior to enrollment
- Current life-threatening illness, medical condition, or organ-system dysfunction that could compromise patient safety or put the study at risk
- Requirement for anticoagulation with warfarin, or for treatment with a strong CYP3A4/5 and/or CYP2D6 inhibitor
- Breast-feeding or pregnant women, or patients for whom there is a risk of conception and who are unable or unwilling to use appropriate contraception (for male and female patients up to 4 months after end of ibrutinib.)
- Previous malignancy with life expectancy less than 6 months or requiring systemic treatment (except colorectal cancer, history of basal cell or squamous carcinoma of skin or pre-invasive carcinoma of the cervix with adequate treatment)
- Known drug abuse/ alcohol abuse
- Severe organ failures or diseases, including: clinically relevant coronary disease, myocardial infarction or any other relevant cardiovascular disorder within 12 months before study entry, severe psychiatric illness and severe infection.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase II Study of INVAC-1 as Treatment of Patients With High-risk Chronic Lymphocytic Leukemia
Phase 2 study to assess the efficacy of INVAC-1, a DNA plasmid encoding a modified human telomerase reverse transcriptas (hTERT) protein, at a dose of 800 µg for 6 cycles 4 weeks apart on Minimal Residual Disease (MRD) eradication rate in the bone marrow, either as a single agent in a high risk "watch and wait" group (group 1 - 42 patients) or in combination with ibrutinib (group 2 - 42 patients), in patients with Chronic Lymphocytic Leukemia (CLL).
Pharmacodynamics and safety will also be assessed.
Read the detailed description
The study will be a phase II, open label, single-arm trial of INVAC-1 at a dose of 800 µg in patients with CLL.
The primary goal of the study is to achieve MRD negativity in each group. 42 patients are to be included in each study group.
Group 1: Untreated high risk "watch and wait" Newly diagnosed patients not eligible for any approved treatment (using NCI Working Group criteria), but having some poor prognosis characteristics (defined by MD Anderson Cancer Center nomogram criteria). Patients will be treated by INVAC-1 for 6 doses at 4-week intervals and then MRD will be assessed. Patients will subsequently be managed as per usual care. For MRD negative patients after INVAC-1 who become MRD+ during follow-up, INVAC-1 can be resumed for 6 months.
Group 2: Ibrutinib treated patients Patients who are receiving ibrutinib as 1st or 2nd line treatment. After at least 12 months of ibrutinib, patients will be assessed for MRD. MRD-positive patients will be treated with ibrutinib + INVAC-1 for 6 months and at the end of the combined treatment period, MRD will be assessed. MRD-negative patients (defined as <0.01% of CLL cells in total cells analyzed) will have the option to stop or continue ibrutinib. Then, they will be followed-up regularly for two years. Patients who become MRD-positive after being MRD-negative will resume ibrutinib single agent.
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Being tested
- INVAC-1
- Keywords
- telomerase, tert, cancer vaccine
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
INVAC-1Biological
Patients are treated by INVAC-1 for 6 cycles at 4-week intervals
| Study group | Role | What they receive |
|---|---|---|
| Group 1: Untreated high risk "watch and wait" | Experimental | Newly diagnosed patients not eligible for any approved treatment (using NCI Working Group criteria), but having some poor prognosis characteristics (defined by MDACC nomogram criteria). Patients will be treated by INVAC-1 for 6 months and then MRD will be assessed. Patients will subsequently be managed as per usual care. For MRD negative patients after INVAC-1 who become MRD+ during follow-up, INVAC-1 can be resumed for one year. Receives: Biological: INVAC-1 |
| Group 2: Ibrutinib treated patients | Experimental | Patients who are receiving ibrutinib as 1st or 2nd line treatment. After at least 12 months of ibrutinib, patients will be assessed for MRD. MRD-positive patients will be treated with ibrutinib + INVAC-1 for 6 months and at the end of the combined treatment period, MRD will be assessed. MRD-negative patients (defined as <0.01% of CLL cells in total cells analyzed) will have the option to stop or continue ibrutinib. Then, they will be followed-up regularly for two years. Patients who become MRD-positive after being MRD-negative will resume ibrutinib single agent. Receives: Biological: INVAC-1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Minimal Residual Disease (MRD) eradication rate in the bone marrow
MRD eradication rate (by standardized 4-color flow cytometry, with a limit of detection of 0.01% CLL cells among total leucocytes in the bone marrow after 6 monthly injections of INVAC-1
Measured: 6 months
Secondary outcomes (9)
MRD eradication rate in blood after 6 monthly injections of INVAC-1
Measured: 6 months
Duration of MRD eradication in bone marrow and blood
Measured: approximately 3 years
Cumulative incidence of partial and complete response by IWCLL 2018
Measured: every 6 months for 3 years
PFS as assessed by investigators according to IWCLL 2018 criteria
Measured: approximately 3 years
Time to next CLL treatment
Measured: approximately 3 years
Overall survival
Measured: approximately 3 years
Adverse events
type, frequency, severity as graded by NCI CTCAE v.4.03
Measured: up to 7 months
Cellular (CD4 & CD8) specific anti hTert response by FACS including cytokine polarization Th1, Th2, Th17
Measured: every 6 months for 3 years
Count of blood circulating CD4, CD8, Treg, NK cells
Measured: every 6 months for 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Aug 2017
- Study start25 Jul 2018
- Primary completion30 Jun 2020
- Study completion30 Jun 2020
Why it stopped: sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Lymphocytic, Chronic, B-CellStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Invectys
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- M.D. Anderson Cancer Center
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03265717
- Sponsor's protocol ID
- INVAC1-CT-201
- Status last verified
- Jul 2020
- First submitted
- 24 Aug 2017
- Last updated
- 8 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of INVAC-1 as Treatment of Patients With High-risk Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT03265717
- Acronym / sponsor ID
- INVAC1-CT-201
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Keywords
- telomerase, tert, cancer vaccine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: sponsor decision
- Enrolment
- 26 participants (actual)
- Lead sponsor
- InvectysIndustry (pharma, biotech, devices)
- Collaborators
- M.D. Anderson Cancer Center
- Study start
- 25 Jul 2018 (actual)
- Primary completion
- 30 Jun 2020 (actual)
- Study completion
- 30 Jun 2020 (actual)
- First posted
- 29 Aug 2017 (actual)
- 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.
Phase 2 study to assess the efficacy of INVAC-1, a DNA plasmid encoding a modified human telomerase reverse transcriptas (hTERT) protein, at a dose of 800 µg for 6 cycles 4 weeks apart on Minimal Residual Disease (MRD) eradication rate in the bone marrow, either as a single agent in a high risk "watch and wait" group (group 1 - 42 patients) or in combination with ibrutinib (group 2 - 42 patients), in patients with Chronic Lymphocytic Leukemia (CLL).
Pharmacodynamics and safety will also be assessed.
Detailed description
The study will be a phase II, open label, single-arm trial of INVAC-1 at a dose of 800 µg in patients with CLL.
The primary goal of the study is to achieve MRD negativity in each group. 42 patients are to be included in each study group.
Group 1: Untreated high risk "watch and wait" Newly diagnosed patients not eligible for any approved treatment (using NCI Working Group criteria), but having some poor prognosis characteristics (defined by MD Anderson Cancer Center nomogram criteria). Patients will be treated by INVAC-1 for 6 doses at 4-week intervals and then MRD will be assessed. Patients will subsequently be managed as per usual care. For MRD negative patients after INVAC-1 who become MRD+ during follow-up, INVAC-1 can be resumed for 6 months.
Group 2: Ibrutinib treated patients Patients who are receiving ibrutinib as 1st or 2nd line treatment. After at least 12 months of ibrutinib, patients will be assessed for MRD. MRD-positive patients will be treated with ibrutinib + INVAC-1 for 6 months and at the end of the combined treatment period, MRD will be assessed. MRD-negative patients (defined as <0.01% of CLL cells in total cells analyzed) will have the option to stop or continue ibrutinib. Then, they will be followed-up regularly for two years. Patients who become MRD-positive after being MRD-negative will resume ibrutinib single agent.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1: Untreated high risk "watch and wait" | Experimental | Biological: INVAC-1Newly diagnosed patients not eligible for any approved treatment (using NCI Working Group criteria), but having some poor prognosis characteristics (defined by MDACC nomogram criteria). Patients will be treated by INVAC-1 for 6 months and then MRD will be assessed. Patients will subsequently be managed as per usual care. For MRD negative patients after INVAC-1 who become MRD+ during follow-up, INVAC-1 can be resumed for one year. |
| Group 2: Ibrutinib treated patients | Experimental | Biological: INVAC-1Patients who are receiving ibrutinib as 1st or 2nd line treatment. After at least 12 months of ibrutinib, patients will be assessed for MRD. MRD-positive patients will be treated with ibrutinib + INVAC-1 for 6 months and at the end of the combined treatment period, MRD will be assessed. MRD-negative patients (defined as <0.01% of CLL cells in total cells analyzed) will have the option to stop or continue ibrutinib. Then, they will be followed-up regularly for two years. Patients who become MRD-positive after being MRD-negative will resume ibrutinib single agent. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Age ≥ 18 years old
- Rai stage 0 - II without active disease according to IWCLL 2018 criteria
- Predicted time to first treatment of ≤3 years according to MDACC nomogram.
- ECOG performance status of 0-2
- Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 1.5 x ULN except Gilbert's Syndrome where a direct bilirubin ≤ 1.5 ULN will be used.
Key exclusion criteria (34 listed)
- Any investigational agent(s) within 4 weeks prior to entry
- Uncontrolled autoimmune hemolytic anemia (Hgb < 11g/deciliter) or idiopathic thrombocytopenic purpura (< 100,000/µl)
- Any previous treatment (chemotherapy, radiotherapy, and/or monoclonal antibodies) intended specifically to treat CLL
- Treatment with corticosteroids other than physiological replacement within the previous week or treatment with immunosuppressive medication within the previous week.
- Major surgery within 4 weeks prior to inclusion
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 |
|---|---|---|
| INVAC-1Patients are treated by INVAC-1 for 6 cycles at 4-week intervals | Biological | Group 1: Untreated high risk "watch and wait", Group 2: Ibrutinib treated patients |
Primary outcome
Minimal Residual Disease (MRD) eradication rate in the bone marrow
Time frame: 6 months
MRD eradication rate (by standardized 4-color flow cytometry, with a limit of detection of 0.01% CLL cells among total leucocytes in the bone marrow after 6 monthly injections of INVAC-1
9 secondary outcomes
MRD eradication rate in blood after 6 monthly injections of INVAC-1
Time frame: 6 months
Duration of MRD eradication in bone marrow and blood
Time frame: approximately 3 years
Cumulative incidence of partial and complete response by IWCLL 2018
Time frame: every 6 months for 3 years
PFS as assessed by investigators according to IWCLL 2018 criteria
Time frame: approximately 3 years
Time to next CLL treatment
Time frame: approximately 3 years
Overall survival
Time frame: approximately 3 years
Adverse events
Time frame: up to 7 months
Cellular (CD4 & CD8) specific anti hTert response by FACS including cytokine polarization Th1, Th2, Th17
Time frame: every 6 months for 3 years
Count of blood circulating CD4, CD8, Treg, NK cells
Time frame: every 6 months for 3 years
Results and safety
The study was stopped early (reason given: sponsor decision). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2020.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing INVAC-1 in people with Leukemia, Lymphocytic, Chronic, B-Cell, run by Invectys at 1 site in United States.
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 19 inclusion and 34 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: stopped early, as of the sponsor's last update on 8 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 phase mean?
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 stopped early (reason given: sponsor decision). Results are not available in the source record.
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?
Minimal Residual Disease (MRD) eradication rate in the bone marrow (time frame: 6 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 8 Jul 2020.