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Dose Escalation Study of CLR 131 in Children, Adolescents, and Young Adults With Relapsed or Refractory Malignant Tumors Including But Not Limited to Neuroblastoma, Rhabdomyosarcoma, Ewings Sarcoma, and Osteosarcoma (CLOVER-2)

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ClinicalTrials.gov Identifier: NCT03478462
Recruitment Status : Recruiting
First Posted : March 27, 2018
Last Update Posted : December 2, 2021
Information provided by (Responsible Party):
Cellectar Biosciences, Inc.

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.

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: An Open-Label, Dose Escalation, Efficacy, and Safety Study of CLR 131 in Children, Adolescents, and Young Adults With Select Solid Tumors, Lymphoma, and Malignant Brain Tumors
Actual Study Start Date : April 30, 2019
Estimated Primary Completion Date : September 2022
Estimated Study Completion Date : December 2024

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

Secondary Outcome Measures :
  1. Identification of recommended phase 2 dose of CLR 131 in children, adolescents, and young adults [ 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) ]
    Dose and regimen to be used in Phase 2 trials of CLR 131 in children, adolescents, and young adults

  2. Determination of preliminary antitumor activity of CLR 131 in children, adolescents, and young adults [ Time Frame: through Day 85 ]
    Response assessment per applicable criteria (e.g., Neuroblastoma Response Criteria (modified); RECIST 1.1; positron emission tomography response criteria in solid tumors (PERCIST); RANO)

  3. Determination of therapeutic activity of CLR 131 in children, adolescents, and young adults [ Time Frame: up to 22 days post initial infusion ]
    Assessment via 131-I/CLR 131 SPECT/CT scans

  4. Determination of event free survival following CLR 131 infusion in children, adolescents, and young adults [ Time Frame: 1 month to 5 years ]
    Time from first infusion of CLR 131 until progression or recurrence of disease

  5. Determination of overall survival following CLR 131 infusion in children, adolescents, and young adults [ Time Frame: 1 month to 5 years ]
    Time from first infusion of CLR 131 until death due to any reason

  6. Determine dosimetry of CLR 131 in children, adolescents, and young adults [ Time Frame: up to 15 days post initial infusion ]
    Assessment of dosimetry via whole body planar imaging

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 25 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. 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.
  • 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 registration 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 registration) or on a steroid tapering regimen. Initiation of steroids per routine care immediately prior to CLR 131 dosing is acceptable.

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 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.

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 ClinicalTrials.gov identifier (NCT number): NCT03478462

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Contact: Kate Oliver 608-327-8125 clinical@cellectar.com

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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    nancy.sweeters@stanford.edu   
Principal Investigator: Allison Pribnow, MD         
United States, New York
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Julia Glade-Bender, MD       gladebej@mskcc.org   
Principal Investigator: Julia Glade-Bender, MD         
United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Lori Backus       lori.backus@cchmc.org   
Principal Investigator: Josephy Pressey, MD         
United States, Texas
Texas Children's Hospital Recruiting
Houston, Texas, United States, 77030
Contact: Kathy McCarthy    832-824-4804    ksmccart@txch.org   
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    PedsHemOncResearch@lists.wisc.edu   
Principal Investigator: Diane Puccetti, MD         
Australia, New South Wales
Children's Hospital at Westmead Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Anna Samolej       Anna.Samolej@health.nsw.gov.au   
Principal Investigator: Dinisha Govender, MBChB         
Canada, Ontario
Hospital for Sick Children Recruiting
Toronto, Ontario, Canada, M5G1X8
Contact: Daniel Morgenstern, MD       nait.info@sickkids.ca   
Principal Investigator: Daniel Morgenstern, MBChir         
Sponsors and Collaborators
Cellectar Biosciences, Inc.
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Study Director: Jarrod Longcor Cellectar Biosciences
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Responsible Party: Cellectar Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT03478462    
Other Study ID Numbers: DCL-17-001
First Posted: March 27, 2018    Key Record Dates
Last Update Posted: December 2, 2021
Last Verified: November 2021
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