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Novel Targeted Radiotherapy in Pediatric Patients With Inoperable Relapsed or Refractory HGG

Primary Purpose

High-Grade Glioma

Status
Not yet recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
CLR 131
Sponsored by
Cellectar Biosciences, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for High-Grade Glioma

Eligibility Criteria

2 Years - 25 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 ≥ 2 years of age and ≤ 25 years of age at time of consent/assent If ≥ age 16 years, Karnofsky performance status of ≥ 60. If < age 16 years, Lansky performance status ≥ 60 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) Absolute neutrophil count ≥ 750/μL 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) Using the bedside Schwartz formula, estimated GFR (creatinine clearance) > 60 ml/min/1.73m2 Alanine aminotransferase < 3 × ULN Bilirubin < 2 × ULN 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. Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol. 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. 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. Patients of childbearing potential must practice an effective method of birth control while participating on this study to avoid possible damage to the fetus. At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging sequence. 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. 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: 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 History of hypersensitivity to iodine 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. Major surgery within 6 weeks of enrollment Known history of human immunodeficiency virus or uncontrolled, serious, active infection Pregnancy or breast-feeding

Sites / Locations

  • Memorial Sloan Kettering Cancer Center
  • Texas Children's Cancer Center, Baylor College of Medicine
  • University of Wisconsin, Carbone Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Pediatric High-Grade Glioma Patients

Arm Description

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.

Outcomes

Primary Outcome Measures

Safety Evaluation of CLR 131
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
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
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
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
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
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
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.

Full Information

First Posted
October 28, 2022
Last Updated
August 26, 2023
Sponsor
Cellectar Biosciences, Inc.
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05610891
Brief Title
Novel Targeted Radiotherapy in Pediatric Patients With Inoperable Relapsed or Refractory HGG
Official Title
A Phase 1b, Open-Label, Study of a Novel Targeted Radiotherapy in Children, Adolescents and Young Adults With Inoperable Relapsed or Refractory High-Grade Glioma
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 1, 2023 (Anticipated)
Primary Completion Date
May 2026 (Anticipated)
Study Completion Date
September 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cellectar Biosciences, Inc.
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
High-Grade Glioma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Model Description
Drug: CLR 131 is a radio-iodinated therapy comprising a core phospholipid ether (PLE) analogue radiolabeled with iodine-131. CLR 131 exploits the tumor-targeting properties of PLEs to provide targeted delivery of radiation to malignant tumor cells and minimizes radiation exposure to normal tissues.
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Pediatric High-Grade Glioma Patients
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
CLR 131
Other Intervention Name(s)
iopofosine I 131
Intervention Description
CLR 131 will be administered IV (intravenously) at a fixed dose based on patients BSA
Primary Outcome Measure Information:
Title
Safety Evaluation of CLR 131
Description
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.
Time Frame
Assessed throughout the study to 1-year post-infusion follow-up period through 3 years following completion of treatment.
Title
Efficacy Evaluation for Progression Free Survival
Description
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.
Time Frame
Day 84 post-infusion follow-up period through 3 years following completion of treatment.
Title
Efficacy Evaluation for Overall Survival
Description
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.
Time Frame
Day 84 post-infusion follow-up period through 3 years following completion of treatment.
Secondary Outcome Measure Information:
Title
Treatment Response of CLR 131
Description
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.
Time Frame
Day 84 post-infusion follow-up period
Title
Dose Determination for CLR 131
Description
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.
Time Frame
Day 84 post-infusion follow-up period
Title
Dosimetry Evaluation for Total Body and Organ
Description
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.
Time Frame
4 hours post-infusion and concluding 4 weeks post-initial imaging
Title
Tumor Response to CLR 131
Description
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.
Time Frame
4 hours post-infusion and concluding 4 weeks post-initial imaging

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 ≥ 2 years of age and ≤ 25 years of age at time of consent/assent If ≥ age 16 years, Karnofsky performance status of ≥ 60. If < age 16 years, Lansky performance status ≥ 60 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) Absolute neutrophil count ≥ 750/μL 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) Using the bedside Schwartz formula, estimated GFR (creatinine clearance) > 60 ml/min/1.73m2 Alanine aminotransferase < 3 × ULN Bilirubin < 2 × ULN 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. Patient or his or her legal representative is judged by the Investigator to have the initiative and means to be compliant with the protocol. 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. 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. Patients of childbearing potential must practice an effective method of birth control while participating on this study to avoid possible damage to the fetus. At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging sequence. 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. 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: 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 History of hypersensitivity to iodine 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. Major surgery within 6 weeks of enrollment Known history of human immunodeficiency virus or uncontrolled, serious, active infection Pregnancy or breast-feeding
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kate Oliver
Phone
608-327-8125
Email
clinical@cellectar.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jarrod Longcor
Organizational Affiliation
Chief Operating Officer
Official's Role
Study Director
Facility Information:
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Texas Children's Cancer Center, Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jennifer Foster, MD
Facility Name
University of Wisconsin, Carbone Cancer Center
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mario Otto, MD

12. IPD Sharing Statement

Plan to Share IPD
Undecided
IPD Sharing Plan Description
The IPD will be made available upon request of NCI, the funding agency partner. This has not yet been decided.

Learn more about this trial

Novel Targeted Radiotherapy in Pediatric Patients With Inoperable Relapsed or Refractory HGG

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