Urgent help for an 11 year old girl

Dear Stephen and all,

I have a question concerning my friend’s daughter. She is a Spanish 11 year old girl. She has been diagnosed with a grade IV medular glioma. She had surgery, but the tumor could not be removed. They just took a biopsy. She has had 30 sessions of radiation and 27 days of temozolomide. Parents are desperatly looking for possible clinical trials that would fit her case. Any suggestions on specific treatments or cocktails would be of much help as well. Even though they live in Spain they would have no problem travelling overseas. We are attaching pathological report, MRI and tractography report.

Please click on the following link.  Once the link takes you to the page of the girl's medical information, click on "Visualizar el estudio" to see her images and "Descargar el informe" to read the medical report:

http://resultados.healthtime.es/PortalPaciente/OpenSharedStudyRequest/a4ac550a-19f7-4d58-99ad-6e1fb2e06ccb

The picture I am including is the report of the pathologist.  It is in Spanish, but I think it is understandable.  If you have any questions, please contact me. 

Thank you all in advance.

Isabel

Advice for a 8 year-old boy with diffuse midline glioma, BRAFV600E and H3K27M mutation

Dear Stephen, dear all,

Anatole, my 8 year-old son has been diagnosed in May 2018 with a diffuse midline glioma on the right thalamus. We are French and based in Stockholm, Sweden. We followed the proposed protocol with the local medical team who works in partnership with Gustave Roussy institute in France but we want to go further now, and we need your advice. The local medical team is not very aware of alternative medication but is willing to help.

Molecular status of the tumour:

BRAFV600E and H3K27M mutation

NF1 and MLH1 mutation

We have little chance to find new targetable alterations by a deeper sequencing. It is possible now that the V600E BRAF mutation is lost in the resistant cells but anyway we do not think it is wise to treat with a V600E BRAF inhibitor which in our experience could speed up tumor growth.  

History:

18/05/09 Diagnosis: MRI tumour size 3.3x3.7x3.7cm, unusual calcification

18/05/16 Biopsy, leading to light hemiparesis

Proton-therapy 18/07/02-18/08/13, 1.8Gy x 30 = 54Gy. Almost fully recovered from hemiparesis

18/09/07 Headaches

18/09/07 MRI tumour size about 4cm

18/09/12 Ventriculostomy

18/09/19 Beginning og Dasatinib (100+70mg/day), after 18/11/06 alternating with Everolimus (5mg/day) every 2 weeks (Biomede protocol)

18/09/22 Beginning of hemiparesis

18/10/03 Wheelchair for walks more than 20m

18/10/12 MRI tumour size 5 to 6cm unsure if pseudoprogession

18/10/22 Beginning of Bevacizumab then once every 2 weeks

18/11/06 Beginning of Everolimus  

18/12/03 MRI tumour size 4 to 5cm unsure if pseudoprogession

18/12/17 Crook for walks less than 20m

19/01/14 MRI tumour size 5x6x5cm

19/01/22 Stop all current chemo (Dasatinib and Everolimus, last Bevacizumab 19/01/02)

24/01/24 PET scan (methyonine)

New plan established by Gustave Roussy Institute: Mebendazol, investigation for debulking of calcification before re-irradiation, eventually ONC201
Any comment on this plan?

Supplements:

Anatole is 30kg 132cm  

D3 vitamin since 18/12/24: escalading from 40µg/d to 100µg/d now

Fish oil since 18/12/24: 1g

Melatonin since 19/01/10: escalading from 2mg/d to 5mg/d now

Turkey tail since 19/01/25: 500mg/d

We plan to add soon:

Longvida Curcumin: 800mg/d

Milk thistle: which dose would you recommend? 

Green tea extract: which dose would you recommend? 

Broccoli sprouts: which dose would you recommend? 

Metformin: Is it worth considering for a child?

Anything else you would find suitable considering his condition (celebrex, chloroquine, clomipramine, berberine, selenium, probiotics, etc?

Diet:

We follow a light low carb diet now (no refined sugar or flour, very limited sugar, no processed food, only bio food). We are planning to begin a ketogenic diet soon, we are ready to change all our habits. We will contact a dietetician specialist in this diet. Anybody else with an experience of ketogenic diet with children?

Thanks to all of you for your precious help, any contribution could help.

Fabrice

Considering treatment options for high grade diffuse midline glioma H3k27m for my 8 year old daughter

Hi all,

Thanks so much to Stephen for your in depth reply to my questions about my 8 year old daughter and invitation to this blog. We moved to Norway in July and my daughter was diagnosed in early September with high grade diffuse midline glioma with H3K27m mutation after an extended biopsy, where it was determined that the tumor was not resectable. She underwent 3 further operations to have a double valve shunt put in to relieve hydrocephalus symptoms. She finished 6 weeks of radiation and Temodal about 10 days ago. The doctors want to start her on Temodal/Lomostine 4 weeks after radiation finished. If we follow this path, we could also have a full molecular analysis done and, upon recurrence, may possibly be able to access a trial using afatinib for BI1200.120, if applicable, or another targeted agent. I would also push for using repurposed drugs in the cocktail approach if possible and our conservative doctors could be convinced. 

We are trying to explore other options, and thanks to Stephen, learned about a new phase I peptide vaccine trial opening for paediatric glioma patients with mutation H3.3K27m based in San Fransisco. It is for patients who have completed 6 weeks of radiation and have not yet started chemo again, which is exactly where we are now. https://clinicaltrials.gov/ct2/show/NCT02960230

I am finding it so difficult to determine what would be the most promising, preferably least toxic option for my daughter. Any input on how promising a peptide vaccine targeted to this kind of mutation could be? Compared with temodar/lomostine/cocktail approach?

Many thanks in advance for your input.

Jeni

Peptide Vaccine for 5 year old with GBM

All-

Thanks to everyone for contributing to this great resource.  First a profile of our daughter's condition and then a question at the end.

Thanks!!!

Our 5 year old:

DOB 9/2/2011

Brooklyn, NY

9/9/2013 admission to:

Weill-Cornell Medical Center

Right neck abscess lanced and drained

March 18th, 2016 admission to:

Weill-Cornell Medical Center

Mass discovered in head after experiencing headaches for a few weeks

Left occipital/parietal brain tumor

Operated 3/19/2016

"Full Gross Resection"

Pathology determines Glioblastoma Multiforme "methylated" 

Transferred to Memorial Sloan Kettering

Photon Radiation treatment for 33 days (Dr. Suzanne Wolden)

Temozolomide chemotherapy for 43 days

MRI on 7/8/2016 'clear' 

'Maintenance' regime of temozolomide prescribed for 12 cycles (5 days chemo/23 days off)

Currently in 5th? cycle 

MRI on 10/5/2016 'clear'

Genetic sequencing/testing

• Cornell _ Precision Medicine

• MSK _ Methylation array

• MSK _ Impact Testing

• Caris Test

Other Diagnosis via 3rd party (non-MSK) bloodwork

• Positive (via Plasma test) for CMV antibodies

• Positive (via DNA test) for Herpes-6 active case

Other Treatments

• Cronaxal (cronaxal.com)

• Cannibas oils (THC/THCa/CBD)

• Chinese Herbs (prescription pending)

• Supplements- Vitamin B, C, D, L-Lysine, Curcumin, sodium selenite, paw paw, cayenne pepper w/garlic, green tea extract, etc.

• Ketogenic diet since appx. June 2016

We are so grateful that our daughter is NED to-date but are considering engaging in an off-label customized peptide vaccine treatment coming out of Tubingen Germany via CeGaT.  Has anyone in this community had any experiences with this?

Treatment description from their literature:

Our personalized peptide vaccination approach aims to train the immune system to recognize

specific “non-self” antigens (neoantigens) which are predicted to be specifically presented by the

patient’s tumor cells. In order to identify tumor-specific mutations, the patient’s tumor and normal

tissue sample (mostly blood) are analyzed using the modern next-generation sequencing technology.

Many of the identified tumor-specific mutations lead to alterations in proteins. Bioinformatic

prediction algorithms are subsequently applied to select those mutated peptides which are most

probably presented on the surface of the tumor cells by the patient-specific HLA molecules and

which have the potential to elicit a strong immune response. These selected peptides are synthesized

and injected as a vaccine in order to stimulate the immune system and to enhance the propagation

and activation of immune cells that specifically attack tumor cells presenting the mutated peptides.

In order to further boost the vaccine specific immune response, an immune stimulatory adjuvant (Leukine) is

co-applied at the injection site.

While they have had good results to-date they have not treated any children.  This obviously concerns us.  Does anyone have any experience with peptide vaccines in children?  The doctors say that theoretically there shouldn't be any difference beyond dosage/body mass.  What are people's thoughts on:

1) The logic of this treatment approach

2) Experiences?

3) Peptides in children

4) Experiences with FDA Personal Use Exemption program / importing off-label drugs from overseas

Again, thanks to everyone for help!

Winston
Brooklyn, NY

Brain stem glioma cocktail

Hi, All!
My 6 years daughter has diagnosed brain stem glioma. Operation and biopsy are not possible.
Standard radiotherapy + temozolamide did not help. In the near future there will be another chemotherapy course: avastin + irinotekanum.
I have read almost everything on the site and have a mess in my head. Could anyone recommend a cocktail for my case?
The main questions:
1. Most of drugs are not permitted for children "officially". What drugs are really should not be used by children?
2. Dosing for 6 years child.

Thanks,
Dmitri