Dose Escalation Study of CLR 131 in Children and Adolescents With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma
- 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 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 who have undergone autologous 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/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 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 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 or on a steroid tapering regimen). 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 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: - 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 Cohort 1 only, 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. n.b. 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. - 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
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.
Trial Phase Phase I
Trial Type Treatment
Cellectar Biosciences, Inc.
- Primary ID DCL-17-001
- Secondary IDs NCI-2018-02444
- Clinicaltrials.gov ID NCT03478462