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GliomaPhase 1NOA-16NCT02454634

Phase I Trial of IDH1 Peptide Vaccine in IDH1R132H-mutated Grade III-IV Gliomas

A Phase 1 study testing IDH1 peptide vaccine in people with Glioma, run by National Center for Tumor Diseases, Heidelberg at 8 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The NOA-16 trial is the first-in-man trial of the IDH1 (isocitrate dehydrogenase type 1) peptide vaccine targeting the IDH1R132H mutation (amino acid exchange from arginine to glutamine at position 132 of IDH1). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Glioma
What is being tested?
IDH1 peptide vaccine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
8 sitesGermany
Study dates
Jun 2015to 19 Sep 2017
Phase
Phase 1
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

  • Patients present with histologically confirmed diagnosis of an IDH1R132H-mutated glioma (with or without measurable residual tumor after tumor resection or biopsy)
  • Histology may be astrocytoma, oligodendroglioma, or oligoastrocytoma WHO grade III or IV
  • Absence of chromosomal 1p/19q co-deletion in the tumor tissue
  • Loss of nuclear ATRX expression in the tumor tissue (partial loss allowed)
  • Availability of tumor tissue for molecular screening (FFPE bulk tissue or biopsy)
  • Patients have received radiotherapy (54 - 60 Gy) alone, 3 cycles of chemotherapy with TMZ (150-200 mg/m2, 5/28 days) or standard combined radiochemotherapy with TMZ prior to enrollment.
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  • Patients should be immunocompetent (i.e. no concomitant treatment with dexamethasone (or equivalent), or receive stable/decreasing steroid levels not exceeding 2 mg/day dexamethasone (or equivalent) during the last 3 days prior to clinical screening; no severe lymphopenia)
  • ≥18 years old, smoking or non-smoking, of any ethnic origin and gender
  • Karnofsky Performance Status ≥ 70
  • Ability of patient to understand character and individual consequences of the clinical trial
  • Evidence of two informed consent documents personally signed and dated by the patient (or a witness in case the patient is unable to write) covering the molecular screening procedure (short IC) and the remaining trial-related procedures (extended IC) and indicating that the patient has been informed of all pertinent aspects of the study and that the patient consents to participate in the trial.
  • Women of child-bearing potential (WOCBP; i.e., those who have not undergone a hysterectomy, bilateral salpingectomy and bilateral oophorectomy or who have not been post-menopausal for at least 24 consecutive months) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of the investigational medicinal product (IMP).
  • WOCBP must be using an effective method of birth control to avoid pregnancy throughout the study and for 24 weeks after the last dose of the IMP. This includes two different forms of effective contraception (e.g., hormonal contraceptive and condom, IUD/IUS and condom) or sterilization, resulting in a failure rate less than 1% per year.
  • Men must be willing and able to use an effective method of birth control throughout the study for up to 24 weeks after the last dose of the IMP, if their sexual partners are WOCBP (acceptable methods see above).
  • Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures

Who cannot join

  • Progressive (incl. pseudoprogression) or recurrent disease after radiation therapy, chemotherapy or radiochemotherapy based on local MRI assessment
  • Previous or concurrent experimental treatment for the tumor. This includes local therapies such as interstitial radiotherapy or local chemotherapy (i.e. BCNU wafers), loco-regional hyperthermia, and antiangiogenic therapy (such as bevacizumab)
  • Antitumor treatment other than standard radiotherapy and/or standard TMZ chemotherapy. Daily metronomic TMZ or intensified dosing scheduled as a substitute for maintenance TMZ cycles are not allowed. (Dose reductions of standard TMZ chemotherapy are allowed.)
  • Abnormal (≥ Grade 2 CTCAE v4.0) laboratory values for hematology, liver and renal function (serum creatinine). In detail the following values apply as exclusion criteria:
  • Hemoglobin < 10 g/dL (6.2 mmol/L)
  • White blood cell count (WBC) decrease (<3.0 x 109/L) or increase (>10.0 x 109/L)
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  • Absolute neutrophil count (ANC) decrease (< 1.5 x 109/L)
  • Platelet count decrease (< 75 x 109/L)
  • Bilirubin > 1.5 x ULN (upper limit of normal according to the performing lab's reference range)
  • ALT > 3 x ULN
  • AST > 3 x ULN
  • GGT > 2.5 x ULN
  • Serum creatinine increase (> 1.5 x ULN)
  • Pregnancy and lactation
  • Patients with history or presence of HIV and/or HBV/HCV
  • Patients with history or known presence of tuberculosis
  • Patients with severe infection(s) or signs/symptoms of infection within 2 weeks prior to the first administration of the study drug
  • Patients who have received a live, attenuated vaccine within 4 weeks prior to the first administration of the study drug
  • Patients with a prior solid organ transplantation or haematopoietic stem cell transplantation
  • History of hypersensitivity to the IMP or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the IMP
  • Participation in other clinical trials or their observation period during the last 30 days before the first administration of the IMP

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

Germany8 sites
  • Charité Berlin, Neurosurgery

    Berlin

  • University Hospital Dresden, Neurosurgery

    Dresden

  • University Hospital Essen, Internal Medicine

    Essen

  • University Hospital Frankfurt, Neurooncology

    Frankfurt am Main

  • University Hospital Freiburg, Neurosurgery

    Freiburg im Breisgau

  • University Hospital Heidelberg, Neurology Clinic

    Heidelberg

  • LMU, University Hospital Munich

    Munich

  • University Hospital Tuebingen, Neurooncology

    Tübingen

Other trials in Germany

About this study

Official title: Targeting IDH1R132H in WHO Grade III-IV IDH1R132H-mutated Gliomas by a Peptide Vaccine - a Phase I Safety, Tolerability and Immunogenicity Multicenter Trial (NOA-16)

The NOA-16 trial is the first-in-man trial of the IDH1 (isocitrate dehydrogenase type 1) peptide vaccine targeting the IDH1R132H mutation (amino acid exchange from arginine to glutamine at position 132 of IDH1). The aim of this trial is to evaluate the safety and tolerability of and immune response to the IDH1 peptide vaccine in patients with IDH1R132H-mutated, WHO grade III-IV gliomas.

Read the detailed description

The patient population will be molecularly defined and include IDH1R132H mutant grade III and IV gliomas without co-deletion of 1p/19q and with loss of alpha-thalassemia/mental retardation syndrome X-linked (ATRX) expression.

Within this trial, the IDH1 peptide vaccine will be administered to 39 patients.

In treatment group 1 vaccination treatment will be done alone starting 4-6 weeks post radiotherapy. In treatment groups 2 and 3 vaccination treatment will be done in parallel with temozolomide (TMZ) chemotherapy starting at day 10 of the 4th TMZ cycle (treatment group 2) or at day 10 of the 1st TMZ cycle post concomitant radiochemotherapy (treatment group 3).

Conditions
Glioma
Being tested
IDH1 peptide vaccine
Keywords
IDH1R132H, peptide vaccine, immunotherapy, IDH1R132H-mutated glioma
Medical subject headings
Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IDH1 peptide vaccineDrug

Study groups in NCT02454634
Study groupRoleWhat they receive
IDH1 peptide vaccineExperimentalThe IDH1 peptide vaccine is a 20mer peptide encompassing the IDH1R132H-mutated region emulsified in Montanide®. It is injected subcutaneously and administered in combination with topical imiquimod. The vaccine is administered 8 times every 2 or 4 weeks.
Receives: Drug: IDH1 peptide vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. safety and tolerability of repeated fixed dose vaccinations of the IDH1 peptide vaccine administered with topical imiquimod (Aldara®) assessed by Regime Limiting Toxicity (RLT).

    Primary safety endpoint is the Regime Limiting Toxicity (RLT).

    Measured: 15 months

  2. immunogenicity of the IDH1 peptide vaccine

    The primary immunogenicity endpoint is the presence of an IDH1R132H-specific T-cell and/or antibody response at any time point during the trial measured by IFN-gamma ELISpot and ELISA, respectively (response Yes/No).

    Measured: 15 months

Secondary outcomes (4)
  1. immunogenicity by assessing the IDH1R132H-specific T-cell and antibody response

    Measured: 15 months

  2. progression-free survival (PFS)

    Measured: 15 months

  3. overall response rate (ORR)

    Measured: 15 months

  4. association between immunogenicity (IDH1R132H-specific T-cell and antibody response) and the clinical outcome parameters (ORR, PFS)

    assessed by Logistic regression and Proportional Hazard models

    Measured: 15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 May 2015 (estimated)
  2. Study startJun 2015
  3. Primary completion19 Sep 2017
  4. Study completion19 Sep 2017

Resources

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02454634
Sponsor's protocol ID
NCT-2013-0216
Other IDs
2014-000503-27, 2014
Acronym
NOA-16
Status last verified
Sep 2017
First submitted
12 May 2015
Last updated
7 Nov 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • Bunse L, Lindner K, Wick A, Freitag A, Lanz LM, Edelmann D, Suwala A, Breckwoldt MO, Harting I, Sahm F, Schlenk RF, Schmitt A, Schnell O, Hense J, Misch M, Krex D, Denk M, Walz J, Steinbach JP, von Deimling A, Schmitt M, Bunse T, Tabatabai G, Bendszus M, Poschke I, Wick W, Platten M. IDH1-mutant vaccine in newly diagnosed astrocytoma: final analysis of the multicenter, single-arm, open-label, first-in-human phase 1 NOA16 trial. Nat Cancer. 2026 Jul 1. doi: 10.1038/s43018-026-01199-y. Online ahead of print.

    PubMed 42387024
  • Platten M, Bunse L, Wick A, Bunse T, Le Cornet L, Harting I, Sahm F, Sanghvi K, Tan CL, Poschke I, Green E, Justesen S, Behrens GA, Breckwoldt MO, Freitag A, Rother LM, Schmitt A, Schnell O, Hense J, Misch M, Krex D, Stevanovic S, Tabatabai G, Steinbach JP, Bendszus M, von Deimling A, Schmitt M, Wick W. A vaccine targeting mutant IDH1 in newly diagnosed glioma. Nature. 2021 Apr;592(7854):463-468. doi: 10.1038/s41586-021-03363-z. Epub 2021 Mar 24.

    PubMed 33762734

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing IDH1 peptide vaccine in people with Glioma, run by National Center for Tumor Diseases, Heidelberg at 8 sites in Germany.

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 15 inclusion and 21 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 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in Germany. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

safety and tolerability of repeated fixed dose vaccinations of the IDH1 peptide vaccine administered with topical imiquimod (Aldara®) assessed by Regime Limiting Toxicity (RLT). (time frame: 15 months). 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?

On the ClinicalTrials.gov record for NCT02454634, which also lists 2 linked publications.

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 Nov 2018.

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