Novel Targeted Radiotherapy in Pediatric Patients With Inoperable Relapsed or Refractory HGG
Study Details
Study Description
Brief Summary
The purpose of this dose finding study is to evaluate the safety and efficacy of 2 different dose levels of CLR 131 in children, adolescents and young adults with relapsed or refractory high-grade glioma (HGG).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
This study is designed to further evaluate the safety and tolerability of CLR 131 at the selected doses in children, adolescents and young adults with relapsed or refractory malignant high-grade glioma. It will also determine the therapeutic activity defined as progression free survival and overall survival, antitumor activity (treatment response) defined as the reduction in tumor volume and identify the recommended Phase 2/3 dose of CLR 131 in children, adolescents and young adults with relapsed or refractory HGG.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pediatric High-Grade Glioma Patients Two dosing cohorts will be explored, 20 mCi/m2 and 25 mCi/m2 and will be administered as two doses separated by 14 days for one cycle. Patients will be eligible to receive a second cycle at the same dose 60 days after receiving the first dose. |
Drug: CLR 131
CLR 131 will be administered IV (intravenously) at a fixed dose based on patients BSA
Other Names:
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Outcome Measures
Primary Outcome Measures
- Safety Evaluation of CLR 131 [Assessed throughout the study to 1-year post-infusion follow-up period through 3 years following completion of treatment.]
Will be assessed by physical examination, performance status, vital signs, laboratory changes over time, and adverse events. Evaluations will use a nonparametric Wilcoxon Signed Rank test and a linear mixed effects modeling will be conducted to evaluate longitudinal changes.
- Efficacy Evaluation for Progression Free Survival [Day 84 post-infusion follow-up period through 3 years following completion of treatment.]
To determine the therapeutic activity defined as Progression Free Survival (PFS) using Kaplan Meier estimator. PFS is defined as the time from treatment initiation until disease progression or death.
- Efficacy Evaluation for Overall Survival [Day 84 post-infusion follow-up period through 3 years following completion of treatment.]
To determine the therapeutic activity defined as Overall Survival (OS) using log-rank test or Cox Hazard model for comparisons. OS is defined as the duration from first infusion of CLR 131 until death due to any reason.
Secondary Outcome Measures
- Treatment Response of CLR 131 [Day 84 post-infusion follow-up period]
Determine antitumor activity (treatment response) defined as the reduction in tumor volume, measured by MRI scans acquired as FLAIR images and based on the RANO criteria for responses.
- Dose Determination for CLR 131 [Day 84 post-infusion follow-up period]
Identify the recommended Phase 2/3 dose of CLR 131 in relapsed pHGG patients based on both safety and efficacy assessments as defined by the primary endpoints concluded from this study.
- Dosimetry Evaluation for Total Body and Organ [4 hours post-infusion and concluding 4 weeks post-initial imaging]
To determine total body and organ dosimetry, together, of CLR 131 in relapsed pHGG patients, measured by conjugate planar whole-body imaging and/or blood collection drawn for radiologic dosimetry analysis for a subset of patients.Organ time/activity integrals will be entered into OLINDA/EXM software57 to produce total body and organ dosimetry values for CLR 131.
- Tumor Response to CLR 131 [4 hours post-infusion and concluding 4 weeks post-initial imaging]
Determine the tumor uptake of CLR 131 and utility of SPECT/CT as a potential diagnostic for response. Images will be reconstructed using quantitative SPECT reconstruction methods with compensation for attenuation, scatter and the full collimator-detector response including septal penetration and scatter. A registered CT image will be used as the attenuation map for the SPECT images. Image data will be converted to activity per cubic centimeters using a sensitivity measurement made using a point source in air.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Previously confirmed (histologically or cytologically) high grade glioma that is clinically or radiographically suspected to be relapsed, refractory, or recurrent for which there are no standard treatment options with curative potential
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≥ 2 years of age and ≤ 25 years of age at time of consent/assent
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If ≥ age 16 years, Karnofsky performance status of ≥ 60. If < age 16 years, Lansky performance status ≥ 60
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Platelets ≥ 75,000/μL (last transfusion, if any, must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
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Absolute neutrophil count ≥ 750/μL
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Hemoglobin ≥ 10 g/dL (last transfusion must be at least 1 week prior to study registration, and, unless deemed medically necessary, no transfusions are allowed between registration and dosing)
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Using the bedside Schwartz formula, estimated GFR (creatinine clearance) > 60 ml/min/1.73m2
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Alanine aminotransferase < 3 × ULN
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Bilirubin < 2 × ULN
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Patients enrolling at total dose levels > 30 millicurie (mCi)/m2 must have availability or ability to collect an autologous hematopoietic stem cell back-up product prior to CLR 131 administration. At minimum, 2 x 10^6/kg cryopreserved CD34+ cells must be available.
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Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol.
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Patient or his or her legal representative has the ability to read, understand, and provide written informed consent for the initiation of any study-related procedures.
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Female patients of childbearing potential must have a negative pregnancy test at screening and within 24 hours of dosing. It is recommended that female caregivers of childbearing potential have a negative pregnancy test within one week of dosing.
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Patients of childbearing potential must practice an effective method of birth control while participating on this study to avoid possible damage to the fetus.
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At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging sequence.
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Patients with previously known neurological deficits must be clinically stable at time of enrollment and able to complete all study related procedures. Patients with documented or newly diagnosed neurological deficits will be enrolled at the investigator's discretion.
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If patient receives steroids for neurological symptom control, the dose must be stable (unchanged for three weeks prior to screening) or on a steroid tapering regimen.
Exclusion Criteria:
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Antitumor therapy or investigational therapy, within 2 weeks of registration. For certain types of radiation (craniospinal, total abdominal, whole lung [spot irradiation to skull-based metastases is not considered craniospinal radiation for the purposes of this study]), at least 3 months must have elapsed. n.b. Patients participating in non-interventional clinical trials (i.e., non-drug) are allowed to participate in this trial
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History of hypersensitivity to iodine
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Any other concomitant serious illness or organ system dysfunction (including cardiac and pulmonary dysfunction) that in the opinion of the Investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug.
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Major surgery within 6 weeks of enrollment
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Known history of human immunodeficiency virus or uncontrolled, serious, active infection
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Pregnancy or breast-feeding
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Memorial Sloan Kettering Cancer Center | New York | New York | United States | 10065 |
| 2 | Texas Children's Cancer Center, Baylor College of Medicine | Houston | Texas | United States | 77030 |
| 3 | University of Wisconsin, Carbone Cancer Center | Madison | Wisconsin | United States | 53705 |
Sponsors and Collaborators
- Cellectar Biosciences, Inc.
- National Cancer Institute (NCI)
Investigators
- Study Director: Jarrod Longcor, Chief Operating Officer
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- DCL-17-001-pHGG
- 13460625