Dose Escalation Study of CLR 131 in Pediatric Relapsed/Refractory Malignant Tumors Including Neuroblastoma and Sarcomas

NCT03478462 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: DCL-17-001
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 8

Brief Summary

The study evaluates CLR 131 in children, adolescents, and young adults 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.

Conditions

Pediatric Solid Tumor; Pediatric Lymphoma; Pediatric Brain Tumor; DIPG; Neuroblastoma; Ewing Sarcoma; Rhabdomyosarcoma; Osteosarcoma

Keywords

medulloblastoma; ependymoma; high-grade glioma; glioblastoma; DIPG; diffuse-intrinsic pontine glioma; ATRT; atypical teratoid rhabdoid tumor; PNET; primitive neuroectodermal tumor; gliosarcoma; gliomatosis cerebri; neuroblastoma; rhabdomyosarcoma; Ewing sarcoma; osteosarcoma; DSRCT; desmoplastic small round cell tumor; sarcoma; malignant germ cell tumor; synovial sarcoma; rare cancer; Wilms tumor; lymphoma; Hodgkin Lymphoma; Non-Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of participants with dose limiting toxicities (DLT)

  DLT will be assessed by physical examination, vital signs, and laboratory values

  up to 64 days

Secondary Outcomes (6)

• Identification of recommended phase 2 dose of CLR 131 in children, adolescents, and young adults

  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)

• Determination of preliminary antitumor activity of CLR 131 in children, adolescents, and young adults

  through Day 85

• Determination of therapeutic activity of CLR 131 in children, adolescents, and young adults

  up to 22 days post initial infusion

• Determination of event free survival following CLR 131 infusion in children, adolescents, and young adults

  1 month to 5 years

• Determination of overall survival following CLR 131 infusion in children, adolescents, and young adults

  1 month to 5 years

Study Arms (1)

CLR 131

EXPERIMENTAL

CLR 131 intravenous administration

Drug: CLR 131

Interventions

CLR 131 DRUG

IV dose of CLR 131, increased/decreased by dose level; single or fractionated dose

Also known as: I-131-CLR1404

CLR 131

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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. Note: patients with diffuse intrinsic pontine glioma (DIPG) may enroll without histological or cytological confirmation.
• ≥ 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 ≥ 8 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 who have undergone autologous or allogeneic bone marrow transplant must be at least 3 months from transplant.
• 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.
• Patients with Pediatric Solid Tumor or Lymphoma
• At least 1 measurable lesion with longest diameter of at least 10 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 10 mm. Patients with neuroblastoma who have detectable disease may enroll provided they meet the requirements of the International Neuroblastoma Response Criteria.

You may not qualify if:

• Patients receiving active treatment for central nervous system metastases or those that are likely to require active treatment during anticipated participation in this trial. Patients with stable brain metastases treated with steroids may enroll at the investigator's discretion
• For solid tumor and lymphoma patients only, central nervous system involvement unless previously treated with surgery, systemic therapy, or radiotherapy with the patient neurologically stable. Patients with metastatic brain tumors that have been previously treated are allowed, provided the patient is neurologically stable (determined at the investigator's discretion).
• Antitumor therapy or investigational therapy, within 2 weeks of dosing. 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. No washout is required for palliative focal radiation. NOTE: Patients participating in non-interventional clinical trials (i.e., non-drug) are allowed to participate in this trial
• 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.

Sponsors & Collaborators

• Cellectar Biosciences, Inc.: lead

Study Sites (8)

Lucile Packard Children's Hospital

Palo Alto, California, 94304, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University

Chapel Hill, North Carolina, 27708, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Children's Hospital at Westmead

Westmead, New South Wales, 2145, Australia

Location

Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

MeSH Terms

Conditions

Neuroblastoma; Sarcoma, Ewing; Rhabdomyosarcoma; Osteosarcoma; Medulloblastoma; Ependymoma; Glioma; Glioblastoma; Diffuse Intrinsic Pontine Glioma; Rhabdoid Tumor; Neuroectodermal Tumors, Primitive; Gliosarcoma; Neoplasms, Neuroepithelial; Desmoplastic Small Round Cell Tumor; Sarcoma; Sarcoma, Synovial; Wilms Tumor; Lymphoma; Hodgkin Disease; Lymphoma, Non-Hodgkin

Interventions

CLR1404

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Astrocytoma; Brain Stem Neoplasms; Infratentorial Neoplasms; Brain Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Complex and Mixed; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplastic Syndromes, Hereditary; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jarrod Longcor

  Cellectar Biosciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 20, 2018
• First Posted: March 27, 2018
• Study Start: April 30, 2019
• Primary Completion (Estimated): August 25, 2026
• Study Completion (Estimated): February 25, 2027
• Last Updated: March 18, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); AU (1); US (6)