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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 (CLOVER-2)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03478462
Recruitment Status : Recruiting
First Posted : March 27, 2018
Last Update Posted : February 25, 2020
Information provided by (Responsible Party):
Cellectar Biosciences, Inc.

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.

Condition or disease Intervention/treatment Phase
Pediatric Solid Tumor Pediatric Lymphoma Pediatric Brain Tumor DIPG Neuroblastoma Ewing Sarcoma Rhabdomyosarcoma Osteosarcoma Drug: CLR 131 Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 30, 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Experimental: CLR 131
CLR 131 intravenous administration
Drug: CLR 131
IV dose of CLR 131, increased/decreased by dose level; single or fractionated dose
Other Name: I-131-CLR1404

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) ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03478462

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Contact: Kate Oliver 608-327-8125

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United States, California
Lucile Packard Children's Hospital Recruiting
Palo Alto, California, United States, 94304
Contact: Nancy Sweeters    650-721-4074   
Principal Investigator: Norman Lacayo, MD         
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Kathy McCarthy    832-824-4804   
Principal Investigator: Jennifer Foster, MD         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: Jenny Weiland    608-890-8070   
Principal Investigator: Mario Otto, MD, PhD         
Australia, New South Wales
Children's Hospital at Westmead Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Anna Samolej   
Contact: Palita Somsri   
Principal Investigator: Dinisha Govender, MBChB         
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Daniel Morgenstern, MD   
Principal Investigator: Daniel Morgenstern, MBChir         
Sponsors and Collaborators
Cellectar Biosciences, Inc.
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Principal Investigator: Mario Otto, MD, PhD University of Wisconsin, Madison
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Responsible Party: Cellectar Biosciences, Inc. Identifier: NCT03478462    
Other Study ID Numbers: DCL-17-001
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: February 25, 2020
Last Verified: February 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cellectar Biosciences, Inc.:
high-grade glioma
diffuse-intrinsic pontine glioma
atypical teratoid rhabdoid tumor
primitive neuroectodermal tumor
gliomatosis cerebri
Ewing sarcoma
desmoplastic small round cell tumor
malignant germ cell tumor
synovial sarcoma
rare cancer
Wilms tumor
Hodgkin Lymphoma
Non-Hodgkin Lymphoma
Additional relevant MeSH terms:
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Brain Neoplasms
Sarcoma, Ewing
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Connective and Soft Tissue
Central Nervous System Neoplasms
Nervous System Neoplasms
Neoplasms by Site
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neuroectodermal Tumors, Primitive, Peripheral
Neuroectodermal Tumors, Primitive
Neoplasms, Neuroepithelial
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms, Glandular and Epithelial
Neoplasms, Nerve Tissue
Neoplasms, Bone Tissue
Neoplasms, Connective Tissue