Anti PD1 Antibody in Diffuse Intrinsic Pontine Glioma

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2015 by Hadassah Medical Organization
Sponsor:
Information provided by (Responsible Party):
Hadassah Medical Organization
ClinicalTrials.gov Identifier:
NCT01952769
First received: September 15, 2013
Last updated: November 3, 2015
Last verified: October 2015
  Purpose
Diffuse pontine gliomas are incurable with currently used treatments. based on data stating that progressive tumors inhibit immune system, would try to enhance immune system activity and tumor cell killing. anti PD1 prevents one of the important mechanisms allowing the tumor to supress the immune system thus we hope it will allow for prolonged control of the tumors

Condition Intervention Phase
DIPG
Biological: MDV9300
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/ II Clinical Trial of MDV9300 (Pidilizumab) in Diffuse Intrinsic Pontine Glioma

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • treatment related toxicity [ Time Frame: monthly for 1 year or if treatment will be continued further due to response-throughout treatment ] [ Designated as safety issue: Yes ]
    Treatment related toxicity according to NCI CTC Version 4.0 will be recorded throughout treatment. a patient with grade 3 or more treatment related toxicity will receive 50% dose reduction. if again grade 3 treatment related toxicity will occur the patient will be taken off study.


Secondary Outcome Measures:
  • progression free survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    tumor measurements according to RANO criteria will be recorded


Other Outcome Measures:
  • overall survival [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    survival after 6 months


Estimated Enrollment: 50
Study Start Date: February 2014
Estimated Study Completion Date: April 2019
Estimated Primary Completion Date: November 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: diffuse pontine glioma
b. DIPG diagnosed based on all the following: i. Symptoms starting less than 6 weeks prior to diagnosis ii. Symptoms include one or more of the following: cranial nerve deficit, cerebellar or long tract dysfunction iii. MRI reveals a lesion infiltrating>70% of the pons
Biological: MDV9300

The study will be done in the following manner:

  1. Evaluation of MDV9300 and radiation-

    1. Cohort A-3 patients: first dose of MDV9300 3mg/m2 .If no toxicity over grade 2-second dose and on -6 mg/kg.
    2. Cohort B -3 patiens: if no toxicity >grade 2 seen in cohort A- start dose will be 6 mg/kg If toxicity> grade 2 in 2 patients or more on a dose of 3 mg/kg the dose in cohort B will be 1 mg/kg during irradiation If toxicity> grade 2 in 2 patients or more on a dose of 1 mg/kg no further concurrent MDV9300 and radiation will be given
  2. Evaluation of MDV9300 and cyclophosphamide

After completion of the first phase (6 patients) a cohort of 15 patients will be accrued. The treatment protocol of this cohort will be as follows:

Following radiation completion , and after recovery from treatment adverse events of grade 2 and higher, the patients will be started on concurrent biweekly MDV9300 and weekly cyclophosphamide 200mg/m2

Other Name: pidilizumab

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  Eligibility

Ages Eligible for Study:   3 Years to 21 Years   (Child, Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  1. Age: 3-21
  2. Diagnosis:

    a. DIPG diagnosed based on all the following: i. Symptoms starting less than 6 weeks prior to diagnosis ii. Symptoms include one or more of the following: cranial nerve deficit, cerebellar or long tract dysfunction iii. MRI reveals a lesion infiltrating>70% of the pons

  3. patient status:

    1. karnofsky or lansky (for children) scale of 60 or more (see appendix I)
    2. liver function:Total bilirubin ≤ 2 ULN, ALT or AST ≤ 2.5 ULN (or < 5 in case of liver impairment)
    3. neutrophils ≥ 1,ooo/mm3, platelets ≥ 100,000/mm3,Lymphocytes ≥1000
    4. Serum creatinine ≤ 1.5 ULN
  4. Life expectancy of at least 4 months
  5. Pregnancy:

    1. Negative pregnancy test in women of childbearing potential
    2. Use of an effective contraceptive method during the whole treatment and up to 3 months after the completion of treatment in males and females
  6. prior informed consent signed

Exclusion criteria:

  1. Severe bacterial, viral or fungal infection (Grade > 2 NCI-CTCAE v.4.0)
  2. Any other serious uncontrolled medical condition (including active bleeding or non healing wound)
  3. Pregnant or breastfeeding women
  4. Participation in another clinical trial up to 10 days prior to study entry
  5. Steroid treatment in a dose more than to 3mg dexamethasone / m2 *
  6. Past infection with HCV
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01952769

Contacts
Contact: Iris Fried, MD 97226777408 ishonet@gmail.com
Contact: Limor Oren, study coordinator Limoro@hadassah.org.il

Locations
Israel
Hadassah Hebrew University Hospital Recruiting
Jerusalem, Israel, 91120
Contact: Iris Fried, MD       ishonet@gmail.com   
Sponsors and Collaborators
Hadassah Medical Organization
  More Information

Responsible Party: Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT01952769     History of Changes
Other Study ID Numbers: antiPD1brainad2- HMO-CTIL 
Study First Received: September 15, 2013
Last Updated: November 3, 2015
Health Authority: Israel : Ministry of Health - Director General

Keywords provided by Hadassah Medical Organization:
anti PD1, malignant glioma. anaplastic astrocytoma,diffuse pontine glioma

Additional relevant MeSH terms:
Glioma
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue

ClinicalTrials.gov processed this record on August 30, 2016