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A phase 1/2 study of DSP-7888 in pediatric patients with relapsed or refractory high grade gliomas

Phase 1
Completed
Conditions
Pediatric high grade glioma
Registration Number
JPRN-jRCT2080223161
Lead Sponsor
Sumitomo Pharma Co.,Ltd.
Brief Summary

In Cohort 1 of Phase 1 part, no adverse events regarded as DLT occurred in any subjects, and DSP-7888 at 3.5 mg/body was tolerated in pediatric patients with malignant glioma. The survival rate was evaluated using the definition of an OS event as death from any cause orinitiation of installing ventilator because of respiratory failure from any cause. In the DIPG subgroup,OS events occurred in 10 of 11 subjects, the 9-month survival rate (90% confidence interval) was 27.3% (7.9 to 56.4).

Detailed Description

Not available

Recruitment & Eligibility

Status
completed
Sex
All
Target Recruitment
18
Inclusion Criteria

1) Patients meeting any of the conditions a) to c) below:
a) Have a diagnosis of diffuse intrinsic pontine glioma on the basis of imaging findings on magnetic resonance imaging (MRI) and clinical course
b) Have histologically or cytologically confirmed glioblastoma
c) Not meeting a) and b) above, but have histologically or cytologically confirmed grade III or IV glioma
2) 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.)
3) Patients aged < 20 years at the time of informed consent
4) 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
5) Patients for whom standard therapy failed or no standard therapy is established
6) 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)
7) Glioblastoma patients and grade III or IV glioma patients must had radiologically evident tumor re-enlargement or recurrence
8) 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.
9) Patients with a life expectancy of 2 months (60 days)
10) Patients with a HLA type of HLA-A*24:02 or A*02:01/06
11) Patients with adequate major organ functions meeting the following criteria on the basis of laboratory data within 28 days before enrollment:
Neutrophil count: 1000/uL
Platelet count: 5.0 x104/uL
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
12) Female patients of childbearing potential must have a negative pregnancy test within 4 weeks (28 days) before enrollment
13) 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

1) Patients with grade 3 infection according to the CTCAE v4.0
2) Patients with a positive test result for HIV antibody, HBs antigen, or HCV antibody
3) Patients with multiple or disseminated primary lesions (Multiple nodules in the same tumor cavity will be acceptable.)
4) Patients with other malignancies
5) 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
6) Patients with uncontrollable complications
7) Patients who underwent allogeneic hematopoietic stem cell transplant
8) 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
9) Pregnant or breastfeeding women
10) 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.
11) Patients with any ongoing CTCAE v4.0 grade 2 adverse effects of prior treatment (excluding alopecia and phlebitis)
12) Patients who received any other investigational product or post-marketing study drug within 4 weeks (28 days) before enrollment
13) Patients with a history of allergy to any oil-based agents
14) Patients who previously received DSP-7888-containing WT1 peptide, or WT1 immunotherapy
15) Patients who are inappropriate for participation in the study for other reasons in the opinion of the investigator or subinvestigator

Study & Design

Study Type
Interventional
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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