Status:
TERMINATED
A Study of BXQ-350 in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG) or Diffuse Midline Glioma (DMG)
Lead Sponsor:
Bexion Pharmaceuticals, Inc.
Collaborating Sponsors:
CTI Clinical Trial and Consulting Services
Conditions:
Diffuse Intrinsic Pontine Glioma
Diffuse Midline Glioma, H3 K27M-Mutant
Eligibility:
All Genders
1-30 years
Phase:
PHASE1
Brief Summary
This study will evaluate the safety of BXQ-350 and determine the maximum tolerated dose (MTD) in children with newly diagnosed DIPG or DMG. All patients will receive BXQ-350 by intravenous (IV) infusi...
Detailed Description
BXQ-350 is a novel anti-neoplastic therapeutic agent configured from two components: Saposin C (SapC), an expressed (human) lysosomal protein, and the phospholipid dioleoylphosphatidyl-serine (DOPS), ...
Eligibility Criteria
Inclusion
- Each subject must meet the following criteria:
- Provide signed, written informed consent prior to the initiation of any study-specific procedures (consent from guardians for minor children and patient assent according to institution and Institutional Review Board (IRB) standards)
- Age ≥ 1 year of age and ≤ 30 years of age at the time of study entry
- Have radiographically suspected or histologically confirmed newly diagnosed DIPG or DMG with the following defining disease characteristics/features:
- Part 1 and Part 2:
- DIPG: radiographic imaging showing a diffuse expansion of the brainstem/pons by a tumor that is poorly defined but abnormally bright in signal on T2-weighted images and abnormally dark on T1-weighted images; contrast enhancement, when present, is typically mild; there may be some indication of necrosis, and the basilar artery is commonly engulfed by tumor.
- DMG: the same imaging characteristics as noted above for DIPG are present, but the lesion can extend superiorly up into the midbrain and thalami, and/or inferiorly to the medulla.
- In cases of disease that is not classic for DIPG or DMG, biopsy may be necessary in order to obtain histological confirmation of eligibility.
- Part 2: newly-diagnosed DIPG or DMG planning to undergo biopsy at the recommendation of the treating physician; to be considered evaluable for PK tissue concentration analysis, tumor samples must have at least 50% viable tumor cells with \<30% necrosis or hemorrhage as determined by the study neuropathologist
- If receiving glucocorticoid therapy: dexamethasone allowed with maximum allowable dose 16mg/day
- Have measurable or non-measurable disease per RANO criteria
- Have Lansky (age 1 - 15) / Karnofsky (age ≥ 16) Performance Score of ≥ 50% or Eastern Cooperative Oncology Group (ECOG) Performance Status (age ≥ 18) of 0 - 2
- Subjects unable to walk because of paralysis, but who can sit without assistance/restraint and control a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Have acceptable liver function defined as:
- Total serum bilirubin ≤ 1.5 x upper limit of normal for the study site (ULN) (in subjects with known Gilbert Syndrome, total bilirubin ≤ 3 x ULN, with direct bilirubin ≤ 1.5 x ULN)
- Aspartate Transaminase (AST), Serum Glutamic Oxaloacetic Transaminase (SGOT), Alanine Transaminase (ALT), Serum Glutamic-Pyruvic Transamine (SGPT) ≤ 3 x ULN (if liver metastases are present, then ≤ 5 x ULN is allowed)
- Serum albumin ≥ 3 grams/deciliter (g/dL)
- Have acceptable renal function defined as:
- Creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥70 milliliters (mL)/min/1.73 meters squared (m2) or a serum creatinine based on age/gender as follows: 1 to \< 2 years: 0.6 (male); 0.6 (female) 2 to \< 6 years: 0.8 (male); 0.8 (female) 6 to \< 10 years: 1 (male); 1 (female) 10 to \< 13 years: 1.2 (male); 1.2 (female) 13 to \< 16 years: 1.5 (male); 1.4 (female)
- 16 years: 1.7 (male);1.4 (female)
- Threshold creatinine values derived from the Schwartz formula for estimating GFR utilizing child length and stature data published by the Center for Disease Control (Schwartz 2009)
- Have acceptable bone marrow function defined as:
- Absolute neutrophil count (ANC) ≥ 1,500 cells/ cubic millimeter (mm3)
- Platelet count ≥ 100,000 cells/mm3 (unsupported, no transfusion within 7 days of enrollment)
- Hemoglobin \> 9.0 g/dL (unsupported, no transfusion within 7 days of enrollment)
- Have acceptable coagulation parameters (anti-coagulation allowed) defined as:
- International normalized ratio (INR) ≤ 2 x ULN unless on anticoagulation or prothrombin time (PT) within normal limits
- Activated partial thromboplastin time (aPTT) within normal limits
- Have a negative serum pregnancy test result at screening (for females of child bearing potential (FCBP); not applicable to subjects who are unable to become pregnant, including those with tubal ligation, bilateral oophorectomy and/or hysterectomy, post-menopausal is defined as \> 12 months since last menstrual cycle)
- FCBP and male subjects whose sexual partner(s) are FCBP must agree to abstain from heterosexual activity or use a double barrier method of contraception (e.g., condom and occlusive cap with spermicide) or highly effective contraception (intrauterine device or system, established hormonal contraceptive methods on a stable dose from the time of the last menstrual cycle, or vasectomized partner with confirmed azoospermia) from the time of study entry to 1 month after the last day of treatment
Exclusion
- Subjects must not meet any of the following criteria:
- Have a concurrent or secondary malignancy
- Have a low-grade glioma (Grade II or less)
- Have received prior treatment with radiation, chemotherapy, anti-neoplastic, or investigational agents
- Have had major surgery other than a minor outpatient procedure within 28 days prior to dose assignment or have not recovered from major side effects of the surgery if more than 4 weeks have elapsed since surgery
- Have poorly controlled hypertension despite the use of antihypertensive agents defined as blood pressure ≥95th percentile for age and weight or \>160/90 on at least 2 repeated determinations on separate days within 2 weeks (14 days) prior to initiation of screening
- Have a history of cardiac dysfunction including:
- myocardial infarction within 6 months prior to initiation of screening
- history of documented congestive heart failure (New York Heart Association functional classification III-IV) within 6 months prior to initiation of screening
- active cardiomyopathy
- electrocardiogram (ECG) with QTc \>470 msec at screening
- echocardiogram with ejection fraction \<50% or a decrease in the left ventricular shortening fraction to \<27%
- Have a known history of Human Immunodeficiency Virus (HIV) seropositivity
- Have active (acute or chronic) or uncontrolled severe infections
- Have active poor wound healing (delayed healing, wound infection or fistula)
- Have evidence of active clinically significant bleed (e.g., gastrointestinal bleed, hemoptysis, or gross hematuria) at screening
- Are pregnant or nursing, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum human chorionic gonadotropin (hCG) laboratory test
- Have a known sensitivity to any component of BXQ-350
- Have other concurrent severe and/or uncontrolled medical condition that would, in the Principal Investigator's judgment contraindicate the subject's participation in the clinical study or obscure assessment of toxicity
Key Trial Info
Start Date :
May 24 2021
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
October 4 2024
Estimated Enrollment :
10 Patients enrolled
Trial Details
Trial ID
NCT04771897
Start Date
May 24 2021
End Date
October 4 2024
Last Update
December 20 2024
Active Locations (3)
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1
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
2
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45226
3
Nationwide Children's
Columbus, Ohio, United States, 43205