Neoplasms

All Conditions

Rare Diseases

Glioma

Glioblastoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

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Anti-Infective Agents

Vaccines

Cyclophosphamide

Molgramostim

Sargramostim

Imiquimod

Immunosuppressive Agents

Immunologic Factors

Antineoplastic Agents, Alkylating

Alkylating Agents

Immunomodulating Agents

Adjuvants, Immunologic

Interferons

One single low-dose i.v. infusion of cyclophosphamide (300mg/m2) prior to the first vaccination as pre-treatment

Six vaccinations with IMA950 plus GM-CSF as adjuvant on 8 pre-defined days from Day 1 to Day 78

IMA950 plus GM-CSF

After Day 78, vaccinations with IMA950 (no GM-CSF) will be given on a monthly basis for up to one year from start of vaccination or until disease progression

IMA950

Imiquimod will be topically applied 10-20 minutes after each vaccination. After the third vaccination onward patients will apply additional imiquimod 24 hours after each vaccination at home on their own

Teri Kreisl, MD

BACKGROUND: Active immunotherapy of cancer is based on the premise that the vaccine raises a cytotoxic immune response to tumor-associated antigens, thereby destroying malignant cells without harming normal cells.

IMA950 is a therapeutic multi-peptide vaccine containing 11 tumor-associated peptides (TUMAPs) found in a majority of glioblastomas, and is designed to activate TUMAP-specific T cells. The use of 11 TUMAPs increases the likelihood of a multi-clonal, highly specific T-cell response against tumor cells leading to decreased likelihood of immune evasion of the tumor by down-regulation of target antigens.

PURPOSE: The primary objective of this study is to determine the safety and tolerability of IMA950 when given with cyclophosphamide, granulocyte macrophage-colony stimulating factor (GM-CSF) and imiquimod in patients with glioblastoma and to determine if IMA950 shows sufficient immunogenicity in these patients.

ELIGIBILITY: Patients with histologically proven GBMs who have completed radiotherapy, and have stable disease following at least 4 cycles of adjuvant temozolomide.

Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma

A Phase 1 Trial of Peptide-Based Glioma Vaccine IMA950 in Patients With Glioblastoma (GBM)

Number of AEs and percentage of patients with AEs (listed per grade and MedDRA preferred terms) will be reported.

Vaccine-induced immune responses to peptides contained in IMA950 will be measured by multimer assay using peripheral blood. Percentage of immune responders (patients with at least one vaccine-induced immune response to IMA950 peptides) and percentage of multi-TUMAP responders (patients with vaccine-induced immune responses to ≥2 peptides in IMA950) will be reported.

Relative frequencies and absolute numbers per µl blood of regulatory T-cells and (if sufficient cells are available) other immune cell populations will be measured from peripheral blood. Focus is on analysis of pre-vaccination frequencies.

Serum levels of proteins and other factors that are indicative of the immune status of the patients will be measured (e.g TGF-beta) and will be correlated with immune response rates and clinical outcome.

Clinical response rates, survival and progression-free survival (PFS) will be followed. PFS at 6 month will be reported.

Corticosteroid levels are not limited in this trial. It will descriptively reported whether the known immunosuppressive effects of corticosteroids are reflected in different immune response rates for patients treated or not treated with corticosteroids.

FACT-Br(4.0) questionnaire will be used to assess HRQL. HRQL scores (total, Trial Outcome Index, subscales) will be reported at baseline. Changes from baseline will also be evaluated.

National Cancer Institute (NCI)

Immatics Biotechnologies GmbH

Oligodendroglioma

Oligoastrocytoma

Pharmaceutical Solutions

Antibodies

Antibodies, Monoclonal

Poly ICLC

Immunoglobulins

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).

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.

poly-ICLC

Varlilumab

Hideho Okada, MD, PhD

Nicholas Butowski, MD

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.

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 IDH1 mutations and mutations in the tumor suppressor gene TP53, located on chromosome 17, the gene product of which is a multifunctional 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.

A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG)

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)

Number of tumor-infiltrating CD4+ and CD8+ T-cells (by flow-cytometry) in IMA950-reactive populations using multi-color flow cytometry will be calculated to determine IMA950-reactive T-cell infiltration in the tumor.

Frequency of CXCL10 expression (by RT-PCR) in IMA950-reactive populations using multi-color flow cytometry will be calculated.

Frequency of CXCL9/10 expression via reverse transcription polymerase chain reaction (RT-PCR) will be calculated.

The number of IMA950-reactive T-cell receptor (TCR) clonotypes via Flow-cytometry will be reported.

OS is defined as the median time from start of treatment to time of death. Patients who have not yet died will be censored at the time of their last follow-up. All patients will be followed for a minimum of 2 years. Product limit (Kaplan-Meier) estimates of the OS functions will be calculated with 95% Greenwood confidence regions.

PFS is defined as the median duration of time from start of treatment to time of progression or death. Patients who have not yet progressed or died will be censored at the time of their last follow-up. All patients will be followed for a minimum of 2 years. Product limit (Kaplan-Meier) estimates of the PFS functions will be calculated with 95% Greenwood confidence regions.

Calculate frequency of PBMC responses against IMA950 in association with OS and PFS

The frequency of PBMC responses in association with the frequency of IMA950 reactive T-cells in the tumor will be calculated.

Tumor objective response rates (ORR) according to Lower-grade gliomas (LGG) Response Assessment in Neuro-Oncology (RANO) if there is measurable tumor after surgery will be reported by response type.

The proportion of participants experiencing Regimen Limiting Toxicity (RLT) in each arm will be tabulated with 95% exact (Clopper-Pearson) confidence intervals.

Percentage of CD4+ cell responses will be compared against IMA950 peptides using the novel 2D multimer flowcytometric analysis.

Percentage of CD8+ T-cell responses will be compared against IMA950 peptides in pre- using the novel 2D multimer flowcytometric analysis.

Magnitude of CD4+ T-cell responses will be compared against IMA950 peptides using the novel 2D multimer flowcytometric analysis.

Magnitude of CD8+ T-cell responses will be compared against IMA950 peptides using the novel 2D multimer flowcytometric analysis.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Peptide-based Glioma Vaccine IMA950 in Patients With Glioblastoma	NCT01403285	Glioblastoma	Cyclophosphamid... IMA950 plus GM-... IMA950 Imiquimod	18 Years -	Immatics Biotechnologies GmbH
A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG)	NCT02924038	Glioma Malignant Gliom... Astrocytoma, Gr... Oligodendroglio... Glioma, Astrocy... Oligoastrocytom...	IMA950 poly-ICLC Varlilumab	18 Years -	University of California, San Francisco
A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG)	NCT02924038	Glioma Malignant Gliom... Astrocytoma, Gr... Oligodendroglio... Glioma, Astrocy... Oligoastrocytom...	IMA950 poly-ICLC Varlilumab	18 Years -	University of California, San Francisco
A Study of Varlilumab and IMA950 Vaccine Plus Poly-ICLC in Patients With WHO Grade II Low-Grade Glioma (LGG)	NCT02924038	Glioma Malignant Gliom... Astrocytoma, Gr... Oligodendroglio... Glioma, Astrocy... Oligoastrocytom...	IMA950 poly-ICLC Varlilumab	18 Years -	University of California, San Francisco

Spots Global Cancer Trial Database for ima950

Every month we try and update this database with for ima950 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for ima950

Every month we try and update this database with for ima950 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for ima950 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.