NCT02454634

Brief 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). 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
39

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jun 2015

Typical duration for phase_1

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 12, 2015

Completed
15 days until next milestone

First Posted

Study publicly available on registry

May 27, 2015

Completed
5 days until next milestone

Study Start

First participant enrolled

June 1, 2015

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

September 19, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

September 19, 2017

Completed
Last Updated

November 7, 2018

Status Verified

September 1, 2017

Enrollment Period

2.3 years

First QC Date

May 12, 2015

Last Update Submit

November 6, 2018

Conditions

Glioma

Keywords

IDH1R132Hpeptide vaccineimmunotherapyIDH1R132H-mutated glioma

Outcome Measures

Primary Outcomes (2)

  • 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).

    15 months

  • 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).

    15 months

Secondary Outcomes (4)

  • immunogenicity by assessing the IDH1R132H-specific T-cell and antibody response

    15 months

  • progression-free survival (PFS)

    15 months

  • overall response rate (ORR)

    15 months

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

    15 months

Study Arms (1)

IDH1 peptide vaccine

EXPERIMENTAL

The 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.

Drug: IDH1 peptide vaccine

Interventions

IDH1 peptide vaccineDRUG
IDH1 peptide vaccine

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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

You may not qualify if:

  • 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.)
  • 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)
  • 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
  • +5 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Charité Berlin, Neurosurgery

Berlin, Germany

Location

University Hospital Dresden, Neurosurgery

Dresden, Germany

Location

University Hospital Essen, Internal Medicine

Essen, Germany

Location

University Hospital Frankfurt, Neurooncology

Frankfurt am Main, Germany

Location

University Hospital Freiburg, Neurosurgery

Freiburg im Breisgau, Germany

Location

University Hospital Heidelberg, Neurology Clinic

Heidelberg, Germany

Location

LMU, University Hospital Munich

Munich, Germany

Location

University Hospital Tuebingen, Neurooncology

Tübingen, Germany

Location

Related Publications (1)

  • 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.

    PMID: 33762734DERIVED

MeSH Terms

Conditions

Glioma

Condition Hierarchy (Ancestors)

Neoplasms, NeuroepithelialNeuroectodermal TumorsNeoplasms, Germ Cell and EmbryonalNeoplasms by Histologic TypeNeoplasmsNeoplasms, Glandular and EpithelialNeoplasms, Nerve Tissue

Study Officials

  • Michael Platten, MD

    University Hospital Heidelberg, Neurology Clinic; Neurooncology Program at the NCT

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 12, 2015

First Posted

May 27, 2015

Study Start

June 1, 2015

Primary Completion

September 19, 2017

Study Completion

September 19, 2017

Last Updated

November 7, 2018

Record last verified: 2017-09

Locations

DE(8)