GliomaPhase 1NCT02924038
A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG)
A Phase 1 study testing IMA950, poly-ICLC and Varlilumab in people with Glioma and Malignant Glioma, run by Nicholas Butowski at 1 site in United States.
Trial summary
This is a pilot, randomized, two arm neoadjuvant vaccine study in human leukocyte antigen-A2 positive (HLA-A2+) adults with World Health Organization (WHO) grade II glioma, for which surgical resection of the tumor is clinically indicated. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioma, Malignant Glioma, Astrocytoma, Grade II
- What is being tested?
- IMA950, poly-ICLC and Varlilumab
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Apr 2017to 31 Dec 2022
- Phase
- Phase 1
- 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 be >= 18 years old.
- Pathological criteria - Participants must have a newly diagnosed or recurrent WHO grade II astrocytoma, oligoastrocytoma or oligodendroglioma that has been histologically confirmed by prior biopsy or surgical resection. If the pathological diagnosis ws made outside of University of California, San Francisco (UCSF), the pathology must be reviewed and confirmed at UCSF.
- Patients must be positive for HLA-A2 based on flow-cytometry or genotyping
- Before enrollment, patients must show non-enhancing T2-FLAIR lesions lesions that are amenable to surgical resection. Surgical resection of at least 0.3 grams of tumor is expected to ensure adequate evaluation of the study endpoints
- Prior radiation therapy (RT) after the initial diagnosis will be allowed but there must be at least 6 months from the completion of RT (or radiosurgery) to signed informed consent.
- Prior chemotherapy and any systemic molecularly targeted anti-tumor therapy will be allowed, and there must be at least 28 days from the last temodar chemotherapy, 42 days for nitrosourea; at least 14 days from the last dose for chemotherapy regimens given continuously or on a weekly basis with limited potential for delayed toxicity.
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- Patients must have a Karnofsky performance status (KPS) of >= 70%.
- Off or low dose (<= 4 mg/day by Decadron) corticosteroid at least two weeks before the first pre-surgical vaccine
- Adequate organ function within 28 days of study registration including: 1) Adequate bone marrow reserve: absolute neutrophil (segmented and bands) count (ANC) >=1.0 x 10^9/L, absolute lymphocyte count >=4.0 x 10^8/L, platelets >=100 x 10^9/L; hemoglobin >=8 g/dL; 2) Hepatic: - Total bilirubin <= 1.5 x upper limit of normal (ULN) and Serum glutamic pyruvic transaminase(SGPT)/ (alanine aminotransferase (ALT)) <=2.5 x upper limit of normal (ULN), and 3) Renal: Normal serum creatinine or creatinine clearance >=60 ml/min/1.73 m^2
- 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.
- Sexually active females of child bearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device (IUD), surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of the vaccination period. Sexually active males must agree to use barrier contraceptive for the duration of the vaccination period.
- Women of child-bearing potential and men must agree to use adequate contraception (ex. Hormonal or barrier method of birth control or abstinence) prior to study entry and for the duration of study participation (until one month after the last vaccine) since the effects of the current regimen on the developing human fetus are unknown. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
- Patient must sign an informed consent document indicating that they are aware of the investigational nature of this study, which includes an authorization for the release of their protected health information
Who cannot join
- Presence of gliomatosis cerebri, cranial or spinal leptomeningeal metastatic disease
- Presence of T1 Gadolinium (Gd)-enhancing lesions (on MRI) suggestive of high-grade glioma
- Pathological diagnosis for the resected tumor demonstrates transformation to higher grade (i.e. WHO grade III or IV) gliomas. If a patient is diagnosed as HGG upon resection after receiving the pre-surgical treatment, the patient will be withdrawn from the study and considered for therapeutic options for HGG (trials for HGG or standard of care). The tumor tissue of such a case would be brought to the lab before the pathological diagnosis is made; and thus would be processed before the lab is informed of the final HGG diagnosis. Because HGG tissue may still reflect the vaccine effects, we will evaluate the tumor tissue to help us develop future approaches for HGG.
- Pregnant women are excluded from this study because IMA950 and poly-ICLC are drugs with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with IMA950 plus poly-ICLC (IMA950-poly-ICLC hereafter) vaccine, breastfeeding should be discontinued if the mother is treated with IMA950- poly-ICLC vaccine
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection (e.g. active or chronic hepatitis B and C), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
- History or current status of immune system abnormalities such as hyperimmunity (e.g., autoimmune diseases) that needed to be treated by systemic therapy, such as immuno-suppressants and hypoimmunity (e.g., myelodysplastic disorders, marrow failures, AIDS, transplant immunosuppression).
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- Any isolated laboratory abnormality suggestive of a serious autoimmune disease (e.g. hypothyroidism): Antinuclear antibody, thyroid-stimulating hormone (TSH), free thyroxine (FT4), rheumatoid factor
- Any condition that could potentially alter immune function (AIDS, multiple sclerosis, diabetes, renal failure)
- Receiving ongoing treatment with immunosuppressive drugs or dexamethasone > 4mg
- Use of any of the following concurrent treatment or medications:
- radiation therapy
- chemotherapy
- interferon (e.g. Intron-A)
- allergy desensitization injections
- growth factors (e.g. Procrit, Aranesp, Neulasta)
- Interleukins (e.g. Proleukin)
- any investigational therapeutic medication
- Prior cancer diagnosis except the following:
- squamous cell cancer of the skin without known metastasis
- basal cell cancer of the skin without known metastasis
- carcinoma in situ of the breast (DCIS or LCIS)
- carcinoma in situ of the cervix
- Any other acute or chronic medical or psychiatric condition or laboratory abnormality that could increase the risk associated with trial participation or trial drug administration or could interfere with the interpretation of trial results and, in the judgment of the investigator, would make the patient inappropriate for entry into the trial.
- Participants with known addiction to any drugs
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California
San Francisco, California, 94143
About this study
Official title: Pilot Randomized Neo-adjuvant Evaluation of Agonist Anti-CD27 Monoclonal Antibody Varlilumab on Immunologic Activities of IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG)
This is a pilot, randomized, two arm neoadjuvant vaccine study in human leukocyte antigen-A2 positive (HLA-A2+) adults with World Health Organization (WHO) grade II glioma, for which surgical resection of the tumor is clinically indicated. Co-primary objectives are to determine: 1) the safety of the novel combination of subcutaneously administered IMA950 peptides and poly-ICLC (Hiltonol) and i.v. administered CDX-1127 (Varlilumab) in the neoadjuvant approach; and 2) whether addition of i.v. CDX-1127 (Varlilumab) increases the response rate and magnitude of CD4+ and CD8+ T-cell responses against the IMA950 peptides in post-vaccine peripheral blood mononuclear cell (PBMC) samples obtained from participating patients.
Read the detailed description
Low-grade gliomas (LGG), the most common of which are pilocytic astrocytomas, diffuse astrocytomas, and oligodendrogliomas are a diverse family of central nervous system (CNS) neoplasms that occur in children and adults. Based on data from the American Cancer Society and Central Brain Tumor Registry of the United States (CBRTUS), approximately 1,800 LGG were diagnosed in 2006, thus representing approximately 10% of newly diagnosed primary brain tumors in the United States. Pilocytic astrocytomas (WHO grade I) are the most common brain tumor in children 5 to 19 years of age. Diffuse astrocytomas and oligodendrogliomas are all considered WHO grade II low grade gliomas (LGG) and are more common in adults. Pilocytic astrocytomas are generally well circumscribed histologically and radiographically and amenable to cure with gross total resection. In contrast, the diffuse astrocytomas and oligodendrogliomas are more infiltrative and less amenable to complete resection. From a molecular genetics standpoint, the most common alterations in LGG are Isocitrate dehydrogenase 1 (IDH1) mutations and mutations in the tumor suppressor gene tumor protein 53 (TP53), located on chromosome 17, the gene product of which is a multi-functional protein involved in the regulation of cell growth, cell death (apoptosis), and transcription. Additionally, several molecular factors are of favorable prognostic significance, particularly the presence of 1p/19q co-deletion and isocitrate dehydrogenase (IDH) mutations.
WHO grade II LGGs are at risk to undergo malignant transformation into more aggressive and lethal WHO grade III or IV high-grade glioma (HGG). Even with a combination of available therapeutic modalities (i.e., surgery, radiation therapy (RT), chemotherapy), the invasive growth and resistance to therapy exhibited by these tumors results in recurrence and death in most patients. Although postoperative RT in LGG significantly improves 5-year progression-free survival (PFS), it does not prolong overall survival (OS) compared with delayed RT given at the time of progression. Early results from a randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine (PCV) chemotherapy for supratentorial adult LGG (RTOG 9802) demonstrated improved PFS in patients receiving PCV plus RT compared RT alone. Nonetheless, PCV is considerably toxic and currently not widely used for management of glioma patients. Although chemotherapy with temozolomide (TMZ) is currently being investigated in LGG patients, it is unknown whether it confers improved OS in these patients. Further, our recent study has indicated that 6 of 10 LGG cases treated with TMZ progressed to HGG with markedly increased exome mutations and, more worrisome, driver mutations in the retinoblastoma tumor suppressor (RB) and Protein kinase B (AKT)-Mechanistic target of rapamycin (mTOR) pathways, with predominant C>T/G>A transitions at CpC and CpT dinucleotides, strongly suggesting a signature of TMZ-induced mutagenesis; this study also showed that in 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, while IDH mutations were the only type of mutations that persisted in the initial and recurrent tumors. These data suggests the possibility that treatment of LGG patients with TMZ may enhance oncogenic mutations and genetic elusiveness of LGG, therefore calling for development of safer and effective therapeutic modalities such as vaccines.
Taken together, LGG are considered a premalignant condition for HGG, such that novel interventions to prevent malignant transformation need to be evaluated in patients with LGG. Immunotherapeutic modalities, such as vaccines, may offer a safe and effective option for these patients due to the slower growth rate of LGG (in contrast with HGG), which should allow sufficient time for multiple immunizations and hence high levels of anti-glioma immunity. Because patients with LGGs are generally not as immuno-compromised as patients with HGG, they may also exhibit greater immunological response to and benefit from the vaccines. Further, the generally mild toxicity of vaccines may improve quality of life compared with chemotherapy or RT.
- Conditions
- Glioma, Malignant Glioma, Astrocytoma, Grade II, Oligodendroglioma, Glioma, Astrocytic, Oligoastrocytoma, Mixed
- Being tested
- IMA950, poly-ICLC, Varlilumab
- Keywords
- low-grade glioma, glioma, immunotherapy, vaccine, WHO grade II
- Medical subject headings
- Glioma, Astrocytoma, Oligodendroglioma, Lymphoma, Follicular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMA950Biological
Also called IMA950 peptides
IMA950 vaccine
poly-ICLCBiological
Also called Hiltonol
poly-ICLC vaccine
VarlilumabBiological
Also called CDX-1127
Intravenous solution
| Study group | Role | What they receive |
|---|---|---|
| IMA950/poly-ICLC subcutaneous (subQ) + Varlilumab IV | Experimental | IMA950 4.96mg and poly-ICLC 1.4mg administered as one formulation subcutaneously followed immediately by a Varlilumab 3mg/kg infusion (intravenously) -23±2 days (about 3 weeks) before the date of scheduled standard-of-care surgery to remove the WHO grade II glioma. Patients will continue receiving IMA950/poly-ICLC subcutaneous injections every week leading up to surgery (Days -16±2, -9±2 and 24-48 hours prior to scheduled surgery) and every 3 weeks after surgery (Weeks A1, A4, A7, A10, A13, A16, A19, A22; defining Week A1 as the first post-surgery vaccine). After surgery, patients will continue receiving a Varlilumab infusion every 6 weeks immediately following the IMA950/poly-ICLC injection (Weeks A1, A7, A13, and A19). Receives: Biological: IMA950; Biological: poly-ICLC; Biological: Varlilumab |
| IMA950/poly-ICLC subQ only | Experimental | IMA950 4.96mg and poly-ICLC 1.4mg administered as one formulation subcutaneously every week leading up to standard-of-care surgery to remove the WHO grade II glioma (Days -23±2, -16±2, -9±2 and 24-48 hours prior to scheduled surgery) and every three weeks after surgery (Weeks A1, A4, A7, A10, A13, A16, A19, A22; defining Week A1 as the first post-surgery vaccine). Patients will not receive Varlilumab. Receives: Biological: IMA950; Biological: poly-ICLC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants Experiencing Regimen Limiting Toxicity (RLT)
The proportion of participants experiencing and RLT defined as an adverse event judged to be possibly, probably or definitely associated with treatment that requires participants to be taken off study and no further injections will be given will be reported.
Measured: up to 2 years
Mean Percentage of CD8+ T-cell Responses in Pre- and Post-vaccine Peripheral Blood Mononuclear Cells (PBMC)
The expansion of IMA950-reactive CD8+ T cell frequencies over post-vaccine periods was assessed by calculating the mean percentage of total IMA950 tetramer-positive CD8+ T cell per available post-vaccine time point. CD8+ T-cell response to the IMA950-epitope is defined to be positive when the percentage of tetramer-positive CD8+ T cells showed a four-fold or higher increase within at least one-time point in the post-vaccine phase relative to the corresponding percentage at the pre-vaccine.
Measured: Up to 2 years
Mean Percentage of CD4+ T-cell Responses in Pre- and Post-vaccine PBMC
The expansion of IMA950-reactive CD4+ T cell frequencies over post-vaccine periods was assessed by calculating the mean percentage of total IMA950 tetramer-positive CD4+ T cell per available post-vaccine time point. CD4+ T-cell response to the IMA950-epitope is defined to be positive when the percentage of tetramer-positive CD4+ T cells showed a four-fold or higher increase within at least one-time point in the post-vaccine phase relative to the corresponding percentage at the pre-vaccine.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2016 (estimated)
- Study start3 Apr 2017
- Primary completion31 Dec 2022
- Study completion31 Dec 2022
Why it stopped: Industry sponsor decision
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nicholas Butowski
- Sponsor type
- University, hospital or other
- Collaborators
- Celldex Therapeutics, National Cancer Institute (NCI)
- Responsible party
- Sponsor-investigator, Nicholas Butowski, University of California, San Francisco
- Investigators
- Hideho Okada, MD, PhD, Principal investigator, University of California, San FranciscoNicholas Butowski, MD, Principal investigator, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02924038
- Sponsor's protocol ID
- 15108
- Other IDs
- NCI-2017-01369, 5R21CA233856-02
- Status last verified
- Jun 2024
- First submitted
- 12 May 2016
- Last updated
- 14 Jun 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Saijo A, Ogino H, Butowski NA, Tedesco MR, Gibson D, Watchmaker PB, Okada K, Wang AS, Shai A, Salazar AM, Molinaro AM, Rabbitt JE, Shahin M, Perry A, Clarke JL, Taylor JW, Daras M, Oberheim Bush NA, Hervey-Jumper SL, Phillips JJ, Chang SM, Hilf N, Mayer-Mokler A, Keler T, Berger MS, Okada H. A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas. Neuro Oncol. 2024 Feb 2;26(2):335-347. doi: 10.1093/neuonc/noad185.
PubMed 37758193
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Randomized Neo-adjuvant Evaluation of Agonist Anti-CD27 Monoclonal Antibody Varlilumab on Immunologic Activities of IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG)
- ClinicalTrials.gov ID
- NCT02924038
- Acronym / sponsor ID
- 15108
- Conditions
- Glioma, Malignant Glioma, Astrocytoma, Grade II, Oligodendroglioma, Glioma, Astrocytic, Oligoastrocytoma, Mixed
- Keywords
- low-grade glioma, glioma, immunotherapy, vaccine, WHO grade II
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Industry sponsor decision
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Nicholas ButowskiUniversity, hospital or other
- Collaborators
- Celldex Therapeutics, National Cancer Institute (NCI)
- Study start
- 3 Apr 2017 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Dec 2022 (actual)
- First posted
- 5 Oct 2016 (estimated)
- Results
- Posted 14 Jun 2024
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 pilot, randomized, two arm neoadjuvant vaccine study in human leukocyte antigen-A2 positive (HLA-A2+) adults with World Health Organization (WHO) grade II glioma, for which surgical resection of the tumor is clinically indicated. Co-primary objectives are to determine: 1) the safety of the novel combination of subcutaneously administered IMA950 peptides and poly-ICLC (Hiltonol) and i.v. administered CDX-1127 (Varlilumab) in the neoadjuvant approach; and 2) whether addition of i.v. CDX-1127 (Varlilumab) increases the response rate and magnitude of CD4+ and CD8+ T-cell responses against the IMA950 peptides in post-vaccine peripheral blood mononuclear cell (PBMC) samples obtained from participating patients.
Detailed description
Low-grade gliomas (LGG), the most common of which are pilocytic astrocytomas, diffuse astrocytomas, and oligodendrogliomas are a diverse family of central nervous system (CNS) neoplasms that occur in children and adults. Based on data from the American Cancer Society and Central Brain Tumor Registry of the United States (CBRTUS), approximately 1,800 LGG were diagnosed in 2006, thus representing approximately 10% of newly diagnosed primary brain tumors in the United States. Pilocytic astrocytomas (WHO grade I) are the most common brain tumor in children 5 to 19 years of age. Diffuse astrocytomas and oligodendrogliomas are all considered WHO grade II low grade gliomas (LGG) and are more common in adults. Pilocytic astrocytomas are generally well circumscribed histologically and radiographically and amenable to cure with gross total resection. In contrast, the diffuse astrocytomas and oligodendrogliomas are more infiltrative and less amenable to complete resection. From a molecular genetics standpoint, the most common alterations in LGG are Isocitrate dehydrogenase 1 (IDH1) mutations and mutations in the tumor suppressor gene tumor protein 53 (TP53), located on chromosome 17, the gene product of which is a multi-functional protein involved in the regulation of cell growth, cell death (apoptosis), and transcription. Additionally, several molecular factors are of favorable prognostic significance, particularly the presence of 1p/19q co-deletion and isocitrate dehydrogenase (IDH) mutations.
WHO grade II LGGs are at risk to undergo malignant transformation into more aggressive and lethal WHO grade III or IV high-grade glioma (HGG). Even with a combination of available therapeutic modalities (i.e., surgery, radiation therapy (RT), chemotherapy), the invasive growth and resistance to therapy exhibited by these tumors results in recurrence and death in most patients. Although postoperative RT in LGG significantly improves 5-year progression-free survival (PFS), it does not prolong overall survival (OS) compared with delayed RT given at the time of progression. Early results from a randomized trial of radiation therapy plus procarbazine, lomustine, and vincristine (PCV) chemotherapy for supratentorial adult LGG (RTOG 9802) demonstrated improved PFS in patients receiving PCV plus RT compared RT alone. Nonetheless, PCV is considerably toxic and currently not widely used for management of glioma patients. Although chemotherapy with temozolomide (TMZ) is currently being investigated in LGG patients, it is unknown whether it confers improved OS in these patients. Further, our recent study has indicated that 6 of 10 LGG cases treated with TMZ progressed to HGG with markedly increased exome mutations and, more worrisome, driver mutations in the retinoblastoma tumor suppressor (RB) and Protein kinase B (AKT)-Mechanistic target of rapamycin (mTOR) pathways, with predominant C>T/G>A transitions at CpC and CpT dinucleotides, strongly suggesting a signature of TMZ-induced mutagenesis; this study also showed that in 43% of cases, at least half of the mutations in the initial tumor were undetected at recurrence, while IDH mutations were the only type of mutations that persisted in the initial and recurrent tumors. These data suggests the possibility that treatment of LGG patients with TMZ may enhance oncogenic mutations and genetic elusiveness of LGG, therefore calling for development of safer and effective therapeutic modalities such as vaccines.
Taken together, LGG are considered a premalignant condition for HGG, such that novel interventions to prevent malignant transformation need to be evaluated in patients with LGG. Immunotherapeutic modalities, such as vaccines, may offer a safe and effective option for these patients due to the slower growth rate of LGG (in contrast with HGG), which should allow sufficient time for multiple immunizations and hence high levels of anti-glioma immunity. Because patients with LGGs are generally not as immuno-compromised as patients with HGG, they may also exhibit greater immunological response to and benefit from the vaccines. Further, the generally mild toxicity of vaccines may improve quality of life compared with chemotherapy or RT.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IMA950/poly-ICLC subcutaneous (subQ) + Varlilumab IV | Experimental | Biological: IMA950, Biological: poly-ICLC, Biological: VarlilumabIMA950 4.96mg and poly-ICLC 1.4mg administered as one formulation subcutaneously followed immediately by a Varlilumab 3mg/kg infusion (intravenously) -23±2 days (about 3 weeks) before the date of scheduled standard-of-care surgery to remove the WHO grade II glioma. Patients will continue receiving IMA950/poly-ICLC subcutaneous injections every week leading up to surgery (Days -16±2, -9±2 and 24-48 hours prior to scheduled surgery) and every 3 weeks after surgery (Weeks A1, A4, A7, A10, A13, A16, A19, A22; defining Week A1 as the first post-surgery vaccine). After surgery, patients will continue receiving a Varlilumab infusion every 6 weeks immediately following the IMA950/poly-ICLC injection (Weeks A1, A7, A13, and A19). |
| IMA950/poly-ICLC subQ only | Experimental | Biological: IMA950, Biological: poly-ICLCIMA950 4.96mg and poly-ICLC 1.4mg administered as one formulation subcutaneously every week leading up to standard-of-care surgery to remove the WHO grade II glioma (Days -23±2, -16±2, -9±2 and 24-48 hours prior to scheduled surgery) and every three weeks after surgery (Weeks A1, A4, A7, A10, A13, A16, A19, A22; defining Week A1 as the first post-surgery vaccine). Patients will not receive Varlilumab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Patients must be >= 18 years old.
- Pathological criteria - Participants must have a newly diagnosed or recurrent WHO grade II astrocytoma, oligoastrocytoma or oligodendroglioma that has been histologically confirmed by prior biopsy or surgical resection. If the pathological diagnosis ws made outside of University of California, San Francisco (UCSF), the pathology must be reviewed and confirmed at UCSF.
- Patients must be positive for HLA-A2 based on flow-cytometry or genotyping
- Before enrollment, patients must show non-enhancing T2-FLAIR lesions lesions that are amenable to surgical resection. Surgical resection of at least 0.3 grams of tumor is expected to ensure adequate evaluation of the study endpoints
- Prior radiation therapy (RT) after the initial diagnosis will be allowed but there must be at least 6 months from the completion of RT (or radiosurgery) to signed informed consent.
Key exclusion criteria (24 listed)
- Presence of gliomatosis cerebri, cranial or spinal leptomeningeal metastatic disease
- Presence of T1 Gadolinium (Gd)-enhancing lesions (on MRI) suggestive of high-grade glioma
- Pathological diagnosis for the resected tumor demonstrates transformation to higher grade (i.e. WHO grade III or IV) gliomas. If a patient is diagnosed as HGG upon resection after receiving the pre-surgical treatment, the patient will be withdrawn from the study and considered for therapeutic options for HGG (trials for HGG or standard of care). The tumor tissue of such a case would be brought to the lab before the pathological diagnosis is made; and thus would be processed before the lab is informed of the final HGG diagnosis. Because HGG tissue may still reflect the vaccine effects, we will evaluate the tumor tissue to help us develop future approaches for HGG.
- Pregnant women are excluded from this study because IMA950 and poly-ICLC are drugs with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with IMA950 plus poly-ICLC (IMA950-poly-ICLC hereafter) vaccine, breastfeeding should be discontinued if the mother is treated with IMA950- poly-ICLC vaccine
- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection (e.g. active or chronic hepatitis B and C), symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
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 |
|---|---|---|
| IMA950Also: IMA950 peptidesIMA950 vaccine | Biological | IMA950/poly-ICLC subQ only, IMA950/poly-ICLC subcutaneous (subQ) + Varlilumab IV |
| poly-ICLCAlso: Hiltonolpoly-ICLC vaccine | Biological | IMA950/poly-ICLC subQ only, IMA950/poly-ICLC subcutaneous (subQ) + Varlilumab IV |
| VarlilumabAlso: CDX-1127Intravenous solution | Biological | IMA950/poly-ICLC subcutaneous (subQ) + Varlilumab IV |
Primary outcome
Proportion of Participants Experiencing Regimen Limiting Toxicity (RLT)
Time frame: up to 2 years
The proportion of participants experiencing and RLT defined as an adverse event judged to be possibly, probably or definitely associated with treatment that requires participants to be taken off study and no further injections will be given will be reported.
Mean Percentage of CD8+ T-cell Responses in Pre- and Post-vaccine Peripheral Blood Mononuclear Cells (PBMC)
Time frame: Up to 2 years
The expansion of IMA950-reactive CD8+ T cell frequencies over post-vaccine periods was assessed by calculating the mean percentage of total IMA950 tetramer-positive CD8+ T cell per available post-vaccine time point. CD8+ T-cell response to the IMA950-epitope is defined to be positive when the percentage of tetramer-positive CD8+ T cells showed a four-fold or higher increase within at least one-time point in the post-vaccine phase relative to the corresponding percentage at the pre-vaccine.
Mean Percentage of CD4+ T-cell Responses in Pre- and Post-vaccine PBMC
Time frame: Up to 2 years
The expansion of IMA950-reactive CD4+ T cell frequencies over post-vaccine periods was assessed by calculating the mean percentage of total IMA950 tetramer-positive CD4+ T cell per available post-vaccine time point. CD4+ T-cell response to the IMA950-epitope is defined to be positive when the percentage of tetramer-positive CD4+ T cells showed a four-fold or higher increase within at least one-time point in the post-vaccine phase relative to the corresponding percentage at the pre-vaccine.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 37758193Saijo A, Ogino H, Butowski NA, Tedesco MR, Gibson D, Watchmaker PB, Okada K, Wang AS, Shai A, Salazar AM, Molinaro AM, Rabbitt JE, Shahin M, Perry A, Clarke JL, Taylor JW, Daras M, Oberheim Bush NA, Hervey-Jumper SL, Phillips JJ, Chang SM, Hilf N, Mayer-Mokler A, Keler T, Berger MS, Okada H. A combinatory vaccine with IMA950 plus varlilumab promotes effector memory T-cell differentiation in the peripheral blood of patients with low-grade gliomas. Neuro Oncol. 2024 Feb 2;26(2):335-347. doi: 10.1093/neuonc/noad185.
- Individual participant dataSharing planned: No
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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.
Hideho Okada, MD, PhD principal investigator
University of California, San Francisco
Nicholas Butowski, MD principal investigator
University of California, San Francisco
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing IMA950, poly-ICLC and Varlilumab in people with Glioma and Malignant Glioma, run by Nicholas Butowski 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 13 inclusion and 24 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 14 Jun 2024. 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 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.
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 14 Jun 2024). 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?
Proportion of Participants Experiencing Regimen Limiting Toxicity (RLT) (time frame: up to 2 years). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02924038, which also lists 1 linked publication.
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 14 Jun 2024.