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History of Changes for Study: NCT03478462
Dose Escalation Study of CLR 131 in Children and Adolescents With Relapsed or Refractory Malignant Brain Cancer, Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma
Latest version (submitted November 30, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 26, 2018 None (earliest Version on record)
2 December 20, 2018 Study Status
3 March 15, 2019 Contacts/Locations and Study Status
4 March 18, 2019 Recruitment Status, Study Status, Contacts/Locations and Oversight
5 March 19, 2019 Contacts/Locations and Study Status
6 July 5, 2019 Study Status, Arms and Interventions, Study Identification and Eligibility
7 September 11, 2019 Conditions and Study Status
8 October 31, 2019 Conditions and Study Status
9 December 3, 2019 Contacts/Locations and Study Status
10 December 17, 2019 Contacts/Locations and Study Status
11 January 20, 2020 Contacts/Locations and Study Status
12 February 24, 2020 Study Status and Contacts/Locations
13 March 15, 2021 Outcome Measures, Study Status, Eligibility, Study Identification and Study Description
14 March 16, 2021 Outcome Measures and Study Status
15 July 23, 2021 Contacts/Locations and Study Status
16 August 3, 2021 Contacts/Locations and Study Status
17 November 30, 2021 Study Status and Contacts/Locations
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Study NCT03478462
Submitted Date:  March 26, 2018 (v1)

Open or close this module Study Identification
Unique Protocol ID: DCL-17-001
Brief Title: Dose Escalation Study of CLR 131 in Children and Adolescents With Relapsed or Refractory Malignant Brain Cancer, Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma
Official Title: A Phase 1, Open-Label, Dose Escalation Study of CLR 131 in Children and Adolescents With Select Solid Tumors, Lymphoma, and Malignant Brain Tumors
Secondary IDs:
Open or close this module Study Status
Record Verification: March 2018
Overall Status: Not yet recruiting
Study Start: July 2018
Primary Completion: September 2020 [Anticipated]
Study Completion: December 2020 [Anticipated]
First Submitted: March 20, 2018
First Submitted that
Met QC Criteria:
March 26, 2018
First Posted: March 27, 2018 [Actual]
Last Update Submitted that
Met QC Criteria:
March 26, 2018
Last Update Posted: March 27, 2018 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Cellectar Biosciences, Inc.
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring: Yes
Open or close this module Study Description
Brief Summary: The study evaluates CLR 131 in children and adolescents with relapsed or refractory malignant solid tumors and lymphoma and recurrent or refractory malignant brain tumors for which there are no standard treatment options with curative potential.
Detailed Description:

Even with standard, highly toxic multimodality therapies and salvage regimen, most pediatric patients with primary metastatic or relapsed solid tumors are confronted with a poor prognosis. For these patients there is currently no accepted successful treatment regimen. There is a need for new drugs, including targeted radiopharmaceuticals, preferably with cancer-specific uptake and broad applicability for these rare pediatric malignancies.

CLR 131 is a radioiodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound (CLR1404) is radiolabeled with the isotope iodine-131 (I-131). CLR 131 has demonstrated tumor selective uptake across numerous adult and pediatric cancer cell types. Therapeutic efficacy has been demonstrated in various pediatric and adult-type cancer xenograft models, confirming the ability of CLR 131 to target tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in relapsed pediatric cancers and initial preclinical and clinical experience with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess CLR 131 in a phase 1 pediatric trial.

Open or close this module Conditions
Conditions: Pediatric Solid Tumor
Pediatric Lymphoma
Pediatric Brain Tumor
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 30 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: CLR 131
Single CLR 131 intravenous administration
Drug: CLR 131
Single IV dose of CLR 131, increased/decreased by dose level
Other Names:
  • I-131-CLR1404
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Number of participants with dose limiting toxicities (DLT)
[ Time Frame: up to 85 days ]

DLT will be assessed by physical examination, vital signs, and laboratory values
Secondary Outcome Measures:
1. Determination of therapeutic activity of CLR 131 in children and adolescents
[ Time Frame: through Day85 ]

Response assessment per applicable criteria (e.g., Neuroblastoma Response Criteria (modified); RECIST 1.1; positron emission tomography response criteria in solid tumors (PERCIST); RANO)
Other Outcome Measures:
1. Identification of recommended phase 2 dose of CLR 131 in children and adolescents
[ Time Frame: until non-tolerated dose is defined; dose escalation decision made upon review of data from a complete cohort (85 days after all subjects in cohort have received infusion) ]

Open or close this module Eligibility
Minimum Age: 2 Years
Maximum Age: 21 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

All Patients

  • Previously confirmed (histologically or cytologically) pediatric solid tumor (e.g., neuroblastoma, sarcoma), lymphoma (including Hodgkin's lymphoma), or malignant brain tumors that are 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 ≤ 21 years of age at time of consent/assent
  • If ≥ age 16, Karnofsky performance status of ≥ 60. If < age 16, 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, age-based serum creatinine within 2 x upper limit of normal (ULN)
  • Alanine aminotransferase < 3 × ULN
  • Bilirubin < 2 × ULN
  • Patients who have undergone autologous bone marrow transplant must be at least 3 months from transplant.
  • Patients enrolling at dose levels > 30 millicurie (mCi)/m2 must have availability or ability to collect an autologous stem cell back-up product prior to CLR 131 administration. At minimum, 2 x 10^6/kg cryopreserved CD34+ cells/kg 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.

Patients with Pediatric Solid Tumor or Lymphoma

  • At least 1 measurable lesion with longest diameter of at least 15 mm. Patients with a lesion(s) that are determined to be Metaiodobenzylguanidine (MIBG) or positron emission tomography (PET) positive may be enrolled at the investigator's discretion, even if not associated with a measurable lesion of at least 15 mm.
  • Patients with known brain metastases must have completed any radiotherapy or systemic treatments for brain metastases prior to enrollment; by investigator assessment be considered stable with no new signs or symptoms for at least 1 month, and on a stable dose of steroids (unchanged for three weeks prior to screening).

Patients with Recurrent or Refractory Brain Tumors

  • At least 1 measurable lesion with longest diameter of at least 10 mm on any imaging sequence.
  • Patients with 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.
  • Patients must be on a stable dose of steroids (unchanged for three weeks prior to screening)

Exclusion Criteria:

  • Patients receiving active treatment for brain metastases or those that are likely to require active treatment during anticipated participation in this trial.
  • Central nervous system involvement unless previously treated with surgery, systemic therapy, or radiotherapy with the patient neurologically stable.
  • 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.
  • Patients previously treated with iodine-131 (131I)-MIBG who have already received a cumulative I-131 dose > 54 mCi/kg or who would exceed 54 mCi/kg by participating in this trial, are not eligible.
  • 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
Open or close this module Contacts/Locations
Central Contact Person: Kate Oliver
Telephone: 608-327-8125
Email: clinical@cellectar.com
Study Officials: Mario Otto, MD, PhD
Principal Investigator
University of Wisconsin, Madison
Locations: United States, Wisconsin
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States, 53792
Contact:Contact: UW Cancer Connect 800-622-8922
Contact:Principal Investigator: Mario Otto, MD, PhD
Contact:Principal Investigator: Lance Hall, MD
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:

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