A Study of DSP-7888 in Pediatric Patients With Relapsed or Refractory High Grade Gliomas

Sponsor

Sumitomo Pharma Co., Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT02750891

Collaborator

(none)

Enrollment

Locations

Arm

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase 1/2, uncontrolled, open-label, multicenter study in patients with recurrent and relapsed diffuse intrinsic pontine glioma, glioblastoma, or grade III or IV glioma.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma Diffuse Intrinsic Pontine Glioma	Drug: DSP-7888	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 1/2 Study of DSP-7888 in Pediatric Patients With Relapsed or Refractory High Grade Gliomas

Actual Study Start Date :

Apr 1, 2016

Actual Primary Completion Date :

Jan 1, 2020

Actual Study Completion Date :

Jan 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DSP-7888	Drug: DSP-7888 Phase1 portion: 1.75 or 3.5 mg/body, Id every 1-4 weeks Phase 2 portion: recommended phase 2 dose, Id every 1-4 weeks

Arm

Intervention/Treatment

Experimental: DSP-7888

Drug: DSP-7888

Phase1 portion: 1.75 or 3.5 mg/body, Id every 1-4 weeks Phase 2 portion: recommended phase 2 dose, Id every 1-4 weeks

Outcome Measures

Primary Outcome Measures

DLT (dose-limiting toxicity) [4 weeks]
Safety and tolerability assessed by dose-limiting toxicity (DLT)
Overall Survival （OS） [24 months]
Participants follow-up for overall survival will occur. Maximum follow-up time is 2 year after the initial administration of the last subject.

Secondary Outcome Measures

Overall Response Rate（ORR） [6 months]
Antitumor effect as assessed according to the Response Assessment in Neuro-Oncology (RANO) criteria
Progression-free survival (PFS) [6 months]
adverse events (AEs) [12 months]
Safety and tolerability assessed by adverse events (AEs)
serious adverse events (SAEs) [12 months]
Safety and tolerability assessed by serious adverse events (SAEs)
DTH （delayed-type hypersensitivity） [6 months]
Explore efficacy related biomarkers assessed by delayed-type hypersensitivity (DTH) reactions to WT1 peptide
WT1 peptide-specific CTL-induction activity [6 months]
Explore efficacy related biomarkers assessed by WT1 peptide-specific CTL-induction activity.
expression of WT1 in biopsy tissues [6 months]
Explore efficacy related biomarkers assessed in biopsy tissues
expression of HLA in biopsy tissues [6 months]
Explore efficacy related biomarkers assessed in biopsy tissues
expression of PD-L1 in biopsy tissues [6 months]
Explore efficacy related biomarkers assessed in biopsy tissues

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 19 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients meeting any of the conditions a) to c) below:
Have a diagnosis of diffuse intrinsic pontine glioma on the basis of imaging findings on magnetic resonance imaging (MRI) and clinical course
Have histologically or cytologically confirmed glioblastoma
Not meeting a) and b) above, but have histologically or cytologically confirmed grade III or IV glioma
Patients who will be able to be hospitalized from the initial dose of DSP-7888 until the end of the post-initial dose observation (In Phase 1 part only, patients may be permitted to have a temporary overnight leave during the hospitalization.)
Patients aged < 20 years at the time of informed consent
Patients for whom either the legally acceptable representative or the patient (if aged ≥ 16 years) have provided written voluntary consent to participation in this study after fully receiving and understanding the information about this study, including study objectives, contents, expected pharmacological actions and effects, and foreseeable risks
Patients for whom standard therapy failed or no standard therapy is established
Diffuse intrinsic pontine glioma patients must received radiotherapy-based treatment or chemotherapy (if radiotherapy is not indicated) at least one cycle and subsequently had tumor enlargement accompanied by tumor-related symptomatic worsening (except for worsening due to dose reduction of steroid therapy for brain edema)
Glioblastoma patients and grade III or IV glioma patients must had radiologically evident tumor re-enlargement or recurrence
Patients with an ECOG PS score of 0 to 2 at enrollment. Patients with a PS score of 3 or 4 due to neurological symptoms associated with the primary disease may be eligible if appropriate in the opinion of the investigator or subinvestigator.
Patients with a life expectancy of 2 months (60 days)
Patients with a HLA type of HLA-A24:02 or A02:01/06
Patients with adequate major organ functions meeting the following criteria on the basis of laboratory data within 28 days before enrollment:

Neutrophil count: 1000/μL Platelet count: 5.0 ×104/μL Hemoglobin: 9.0 g/dL Serum creatinine: 2-fold the upper limit of the normal range of the study site (ULN) Total bilirubin: 2-fold the ULN AST, ALT: 3-fold the ULN

Female patients of childbearing potential must have a negative pregnancy test within 4 weeks (28 days) before enrollment
Female patients of childbearing potential and male patients with female partners of childbearing potential must agree to use appropriate contraception from the time of consent until 180 days after the last dose of the study drug to avoid pregnancy

Exclusion Criteria:

Patients with grade 3 infection according to the CTCAE v4.0
Patients with a positive test result for HIV antibody, HBs antigen, or HCV antibody
Patients with multiple or disseminated primary lesions (Multiple nodules in the same tumor cavity will be acceptable.)
Patients with other malignancies
Patients with significant diseases at enrollment that may affect study treatment, such as New York Heart Association (NYHA) Functional Class III or IV heart disease, CTCAE v4.0 grade 3 arrhythmia, angina pectoris, abnormal electrocardiogram findings, interstitial pneumonia or pulmonary fibrosis
Patients with uncontrollable complications
Patients who underwent allogeneic hematopoietic stem cell transplant
Patients who received any of the following treatments within the specified period before enrollment

Nitrosoureas, mitomycin C: <42 days
Chemotherapy (including molecular-targeted drugs), radiotherapy: <21 days
Surgery, blood transfusion, erythropoiesis-stimulating drugs, endocrine therapy, immunotherapy (including biological response modifier [BRM] therapy): <14 days

Pregnant or breastfeeding women
Patients with concurrent autoimmune disease or a history of chronic or recurrent autoimmune disease, or patients who require long-term systemic steroid therapy (excluding therapy given on a PRN basis). However, steroid therapy for brain edema (prednisolone-equivalent dose of 30 mg/m2) and steroid replacement therapy at a physiologic dose will be acceptable.
Patients with any ongoing CTCAE v4.0 grade 2 adverse effects of prior treatment (excluding alopecia and phlebitis)
Patients who received any other investigational product or post-marketing study drug within 4 weeks (28 days) before enrollment
Patients with a history of allergy to any oil-based agents
Patients who previously received DSP-7888-containing WT1 peptide, or WT1 immunotherapy
Patients who are inappropriate for participation in the study for other reasons in the opinion of the investigator or subinvestigator

Contacts and Locations

Locations

	Site	City	State	Country
1	National Hospital Organization Nagoya Medical Center	Nagoya	Aichi	Japan
2	Kanagawa Children's Medical Center	Yokohama	Kanagawa	Japan
3	Osaka University Hospital	Suita	Osaka	Japan
4	National Center for Child Health and Development	Setagaya	Tokyo	Japan
5	Hiroshima University Hospital	Hiroshima		Japan
6	Osaka City General Hospital	Osaka		Japan