Malignant GliomaPhase 1/2NCT00766753
Vaccination-Dendritic Cells With Peptides for Recurrent Malignant Gliomas
A Phase 1/2 study testing Dendritic vaccine pulsed with multiple peptides, The first booster vaccine phase: and The second booster vaccine phase: in people with Malignant Glioma, run by Frank Lieberman at 1 site in United States.
Trial summary
This is a single-institution Phase I/II study designed to evaluate the safety and induction of an immune response, and preliminary clinical response of vaccinations with Type-1 alpha-DCs (alpha-DC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Glioma
- What is being tested?
- Dendritic vaccine pulsed with multiple peptides, The first booster vaccine phase: and The second booster vaccine phase:
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2006to Jun 2016
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Patients must have a histologically confirmed
- recurrent glioblastoma (GBM)
- anaplastic astrocytoma (AA)
- anaplastic oligodendroglioma (AO)
- anaplastic mixed oligoastrocytoma (AMO)
- other anaplastic glioma
Show all 27Show fewer
- Patients must have received prior external beam radiotherapy and/or chemotherapy unless patients refused the options.
- Patients may have had treatment for no more than 2 prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy).
- Patients must be HLA-A2 positive.
- All patients must sign an informed consent document indicating that they are aware of the investigational nature of this study.
- Patients must sign an authorization for the release of their protected health information.
- Patients must be > 18 years old, and with a life expectancy > 8 weeks. -Patients must have a Karnofsky performance status of > 60.
- Patients must have recovered from the toxic effects of prior therapy: 4 weeks from any investigational agent, 4 weeks from prior cytotoxic therapy and/or at least two weeks from vincristine, 4 weeks from nitrosoureas, 3 weeks from procarbazine administration, and 1 week for non-cytotoxic agents, e.g., interferon, tamoxifen, thalidomide, cis-retinoic acid, etc. (radiosensitizer does not count). Any questions related to the definition of non-cytotoxic agents should be directed to the principal investigator.
- Patients must not have any disease that will obscure toxicity or dangerously alter drug metabolism.
- Patients must not have any serious concurrent medical illness.
- Documented negative serum beta-HCG for female patients of child-bearing age.
- Patients must be free of systemic infection. Subjects with active infections (whether or not they require antibiotic therapy) may be eligible after complete resolution of the infection. Subjects on antibiotic therapy must be off antibiotics for at least 7 days before beginning treatment.
- Patients must have adequate organ function as measured by:
- Hematopoietic:
- granulocytes at least 2500/mm3
- lymphocytes at least 1000/mm3
- platelets at least 100,000/mm3
- hemoglobin at least 10.0 g/dL
- Cardiac: Asymptomatic or, if symptomatic, then left ventricular ejection fraction at rest must be at least 50% or within the normal range of the institution. A cardiology clearance will be required for LV ejection fraction 50%.
- Hepatic: AST, ALT, GGT, LDH, Alk phos within 2.5 x upper normal limit and total bilirubin no greater than 2.0 mg/dL.
- Renal: Serum creatinine up to 1.5 x upper normal limit.
- Pretreatment baseline evaluations for laboratory parameters must be obtained within 10 to 18 days of subject registration.
Who cannot join
- Pregnant or breast-feeding.
- Presence of metastatic disease.
- Active bacterial, viral or fungal infections. Subjects with active infections (whether or not they require antibiotic therapy) may be eligible after complete resolution of the infection. Subjects on antibiotic therapy must be off antibiotics for at least 7 days before beginning treatment.
- Chemotherapy, biologic therapy or radiation therapy less than one month prior to study entry.
- History or presence of autoimmune disease.
- Use of immunosuppressives within 4 weeks prior to study entry or anticipated use of immunosuppressive agents. Minimum doses of corticosteroid (dexamethasone up to 4 mg/day) is permitted.
- Subjects with uncontrolled pain. -Subjects who have sensitivity to drugs to provide local anesthesia.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
About this study
Official title: A Phase I/II Evaluation of Vaccination With Type 1 Dendritic Cells Pulsed With Multiple Peptides in the Treatment of HLA-A2 Positive Patients With Recurrent Malignant Gliomas
This is a single-institution Phase I/II study designed to evaluate the safety and induction of an immune response, and preliminary clinical response of vaccinations with Type-1 alpha-DCs (alpha-DC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. Approximately 30 subjects will be enrolled in this study at UPMC/UPCI Hillman Cancer Center. The study participants in this trial will be HLA-A2 positive male or female adults over 18 years of age. The primary objective is to establish the safety of this approach. The endpoints will be to determine the maximum tolerated dose (MTD) of alpha-DC1 vaccines in combination with a fixed dose of poly-ICLC, using standard criteria and close clinical followups. The secondary objectives are 1) to assess the immunological response against GAAs in patients with recurrent malignant gliomas immunized with DCs loaded with GAA-derived peptides using enzyme-linked immuno-spot (ELISPOT), delayed-type hypersensitivity (DTH) and tetramer assays; and 2) to assess the preliminary anti-tumor clinical activity of the vaccines as measured by radiological response (MRI), overall survival, and 4- and 6-month progression-free survival (PFS).
Read the detailed description
This is a single-institution Phase I/II study designed to evaluate the safety, the induction of an immune response, and the preliminary clinical response of vaccinations with Type-1 αDCs (αDC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. The hypothesis is that this form of vaccines in combination with poly-ICLC treatment will prove to be safe, and will induce potent anti-glioma immune responses.
The primary objective is to establish the safety of the approach.
The secondary objectives are to 1) assess the immunological response against GAAs in patients with recurrent malignant gliomas immunized with DCs loaded with GAA-derived peptides using enzyme-linked immuno-spot (ELISPOT), delayed-type hypersensitivity (DTH) and tetramer assays and 2) assess the preliminary anti-tumor clinical activity of the vaccines as measured by radiological response (MRI), overall survival, and four- and six-month progression-free survival (PFS).
- Conditions
- Malignant Glioma
- Being tested
- Dendritic vaccine pulsed with multiple peptides, The first booster vaccine phase:, The second booster vaccine phase:
- Keywords
- HLA-A2 positive, Malignant Gliomas, Vaccine
- Medical subject headings
- Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Dendritic vaccine pulsed with multiple peptidesBiological
Subjects will receive four (4) injections of the vaccine into the lymph nodes. Injection is guided by ultrasonography. Subjects will receive the first cycle of vaccine in the right groin. Two weeks after the first vaccine, subjects receive the same vaccine at the left groin, followed by the 3rd and the 4th vaccines in the left and right armpits, respectively, with two-week intervals. Each injection contains 0.2cc (less than 1/20th of a teaspoon) of a saline solution containing the vaccine cell mixture.
The first booster vaccine phase:Biological
This phase will begin at week 13. These subjects will be treated with additional vaccinations every 4 weeks to a maximum of 5 vaccine injections and, if poly-ICLC is available from the supplier starting on the day of the first additional vaccine and twice/week for 8 injections following each additional vaccine. If poly-ICLC supply is not available from the supplier, DC vaccines only will be given in the booster phases.
The second booster vaccine phase:Biological
At week 33, following the completion of 5 additional vaccines, if participants demonstrate stable disease or positive clinical response, if poly-ICLC supply is still available, participants will be offered additional DC-vaccines and poly-ICLC treatment. The second phase booster vaccines can be continued as long as the patient shows continued positive response or stable disease (both radiological and clinically) with no major adverse events, and as long as funding is available for the study. DC vaccines in this phase will be administered every 6 months+/- 2 weeks.
2). Poly-ICLC at 10µg/kg and up to 1640 µg/injection will be administered intramuscularly (i.m.) on the day of each booster DC vaccine. Poly-ICLC will be administered weekly thereafter for twice (at one week and two weeks after each vaccine) (e.g. if the previous DC vaccine was administered on a Thursday, subsequent poly-ICLC will be administered on the next two Thursdays
| Study group | Role | What they receive |
|---|---|---|
| Single | Experimental | All consenting, eligible subjects receive the intervention Receives: Biological: Dendritic vaccine pulsed with multiple peptides; Biological: The first booster vaccine phase:; Biological: The second booster vaccine phase: |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced Treatment-related Dose Limiting Toxicities (DLT)
Number of participants who experienced treatment-related Dose Limiting Toxicities (DLT) at any dose level.
Measured: up to 8 weeks
Median Time To Progression
Median number of months until disease progression. Tumor size was assessed using magnetic resonance imaging (MRI) scans with contrast enhancement to detect change from baseline.
Measured: At baseline, 9, 17, 25, and 33 weeks, and every 3 months; up to 23 months
Secondary outcomes (2)
12-month- Progression Free Survival (PFS)
Number of patients with progression-free status lasting at least 12 months
Measured: Up to 12 months
Overall Survival (OS)
Time interval from start of treatment until date of death.
Measured: Up to 102 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Oct 2008 (estimated)
- Study startDec 2006
- Primary completionSep 2009
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Malignant GliomaStudies 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
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- Frank Lieberman
- Sponsor type
- University, hospital or other
- Collaborators
- Oncovir, Inc.
- Responsible party
- Sponsor-investigator, Frank Lieberman, University of Pittsburgh
- Investigators
- Frank Lieberman, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00766753
- Sponsor's protocol ID
- 05-115
- Other IDs
- NIH/NINDS/NCI, 1R21CA117152-01A2
- Status last verified
- Jan 2018
- First submitted
- 23 Jun 2008
- Last updated
- 7 Feb 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Evaluation of Vaccination With Type 1 Dendritic Cells Pulsed With Multiple Peptides in the Treatment of HLA-A2 Positive Patients With Recurrent Malignant Gliomas
- ClinicalTrials.gov ID
- NCT00766753
- Acronym / sponsor ID
- 05-115
- Conditions
- Malignant Glioma
- Keywords
- HLA-A2 positive, Malignant Gliomas, Vaccine
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- Frank LiebermanUniversity, hospital or other
- Collaborators
- Oncovir, Inc.
- Study start
- Dec 2006 (actual)
- Primary completion
- Sep 2009 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 6 Oct 2008 (estimated)
- Results
- Posted 11 May 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a single-institution Phase I/II study designed to evaluate the safety and induction of an immune response, and preliminary clinical response of vaccinations with Type-1 alpha-DCs (alpha-DC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. Approximately 30 subjects will be enrolled in this study at UPMC/UPCI Hillman Cancer Center. The study participants in this trial will be HLA-A2 positive male or female adults over 18 years of age. The primary objective is to establish the safety of this approach. The endpoints will be to determine the maximum tolerated dose (MTD) of alpha-DC1 vaccines in combination with a fixed dose of poly-ICLC, using standard criteria and close clinical followups. The secondary objectives are 1) to assess the immunological response against GAAs in patients with recurrent malignant gliomas immunized with DCs loaded with GAA-derived peptides using enzyme-linked immuno-spot (ELISPOT), delayed-type hypersensitivity (DTH) and tetramer assays; and 2) to assess the preliminary anti-tumor clinical activity of the vaccines as measured by radiological response (MRI), overall survival, and 4- and 6-month progression-free survival (PFS).
Detailed description
This is a single-institution Phase I/II study designed to evaluate the safety, the induction of an immune response, and the preliminary clinical response of vaccinations with Type-1 αDCs (αDC1) loaded with glioma-associated antigen (GAA) epitopes and administration of poly-ICLC in patients with recurrent malignant gliomas. The hypothesis is that this form of vaccines in combination with poly-ICLC treatment will prove to be safe, and will induce potent anti-glioma immune responses.
The primary objective is to establish the safety of the approach.
The secondary objectives are to 1) assess the immunological response against GAAs in patients with recurrent malignant gliomas immunized with DCs loaded with GAA-derived peptides using enzyme-linked immuno-spot (ELISPOT), delayed-type hypersensitivity (DTH) and tetramer assays and 2) assess the preliminary anti-tumor clinical activity of the vaccines as measured by radiological response (MRI), overall survival, and four- and six-month progression-free survival (PFS).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single | Experimental | Biological: Dendritic vaccine pulsed with multiple peptides, Biological: The first booster vaccine phase:, Biological: The second booster vaccine phase:All consenting, eligible subjects receive the intervention |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (27 listed)
- Patients must have a histologically confirmed
- Patients must have received prior external beam radiotherapy and/or chemotherapy unless patients refused the options.
- Patients may have had treatment for no more than 2 prior relapses. Relapse is defined as progression following initial therapy (i.e. radiation +/- chemo if that was used as initial therapy).
- Patients must be HLA-A2 positive.
- All patients must sign an informed consent document indicating that they are aware of the investigational nature of this study.
Key exclusion criteria (7 listed)
- Pregnant or breast-feeding.
- Presence of metastatic disease.
- Active bacterial, viral or fungal infections. Subjects with active infections (whether or not they require antibiotic therapy) may be eligible after complete resolution of the infection. Subjects on antibiotic therapy must be off antibiotics for at least 7 days before beginning treatment.
- Chemotherapy, biologic therapy or radiation therapy less than one month prior to study entry.
- History or presence of autoimmune disease.
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 |
|---|---|---|
| Dendritic vaccine pulsed with multiple peptidesSubjects will receive four (4) injections of the vaccine into the lymph nodes. Injection is guided by ultrasonography. Subjects will receive the first cycle of vaccine in the right groin. Two weeks after the first vaccine, subjects receive the same vaccine at the left groin, followed by the 3rd and the 4th vaccines in the left and right armpits, respectively, with two-week intervals. Each injection contains 0.2cc (less than 1/20th of a teaspoon) of a saline solution containing the vaccine cell mixture. | Biological | Single |
| The first booster vaccine phase:This phase will begin at week 13. These subjects will be treated with additional vaccinations every 4 weeks to a maximum of 5 vaccine injections and, if poly-ICLC is available from the supplier starting on the day of the first additional vaccine and twice/week for 8 injections following each additional vaccine. If poly-ICLC supply is not available from the supplier, DC vaccines only will be given in the booster phases. | Biological | Single |
| The second booster vaccine phase:At week 33, following the completion of 5 additional vaccines, if participants demonstrate stable disease or positive clinical response, if poly-ICLC supply is still available, participants will be offered additional DC-vaccines and poly-ICLC treatment. The second phase booster vaccines can be continued as long as the patient shows continued positive response or stable disease (both radiological and clinically) with no major adverse events, and as long as funding is available for the study. DC vaccines in this phase will be administered every 6 months+/- 2 weeks. 2). Poly-ICLC at 10µg/kg and up to 1640 µg/injection will be administered intramuscularly (i.m.) on the day of each booster DC vaccine. Poly-ICLC will be administered weekly thereafter for twice (at one week and two weeks after each vaccine) (e.g. if the previous DC vaccine was administered on a Thursday, subsequent poly-ICLC will be administered on the next two Thursdays | Biological | Single |
Primary outcome
Number of Participants Who Experienced Treatment-related Dose Limiting Toxicities (DLT)
Time frame: up to 8 weeks
Number of participants who experienced treatment-related Dose Limiting Toxicities (DLT) at any dose level.
Median Time To Progression
Time frame: At baseline, 9, 17, 25, and 33 weeks, and every 3 months; up to 23 months
Median number of months until disease progression. Tumor size was assessed using magnetic resonance imaging (MRI) scans with contrast enhancement to detect change from baseline.
2 secondary outcomes
12-month- Progression Free Survival (PFS)
Time frame: Up to 12 months
Overall Survival (OS)
Time frame: Up to 102 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Online database of trials; this links the viewer to the UPMC websiteLink provided by the sponsor.
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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.
Frank Lieberman, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Dendritic vaccine pulsed with multiple peptides, The first booster vaccine phase: and The second booster vaccine phase: in people with Malignant Glioma, run by Frank Lieberman 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 27 inclusion and 7 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: finished, as of the sponsor's last update on 7 Feb 2018. 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 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?
Yes. Results are posted in the registry (first posted 11 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Participants Who Experienced Treatment-related Dose Limiting Toxicities (DLT) (time frame: up to 8 weeks). The study lists 2 primary outcomes in all. 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 7 Feb 2018.