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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

NCT03478462

Description:

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.

Related Conditions:
  • Lymphoma
  • Malignant Central Nervous System Neoplasm
  • Neuroblastoma
  • Sarcoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: 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
  • 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

Clinical Trial IDs

  • ORG STUDY ID: DCL-17-001
  • NCT ID: NCT03478462

Conditions

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

Interventions

DrugSynonymsArms
CLR 131I-131-CLR1404CLR 131

Purpose

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
CLR 131ExperimentalCLR 131 intravenous administration
  • CLR 131

Eligibility 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. 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.
      
Maximum Eligible Age:25 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with dose limiting toxicities (DLT)
Time Frame:up to 64 days
Safety Issue:
Description:DLT will be assessed by physical examination, vital signs, and laboratory values

Secondary Outcome Measures

Measure: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)
Safety Issue:
Description:Dose and regimen to be used in Phase 2 trials of CLR 131 in children, adolescents, and young adults
Measure:Determination of preliminary antitumor activity of CLR 131 in children, adolescents, and young adults
Time Frame:through Day 85
Safety Issue:
Description:Response assessment per applicable criteria (e.g., Neuroblastoma Response Criteria (modified); RECIST 1.1; positron emission tomography response criteria in solid tumors (PERCIST); RANO)
Measure:Determination of therapeutic activity of CLR 131 in children, adolescents, and young adults
Time Frame:up to 22 days post initial infusion
Safety Issue:
Description:Assessment via 131-I/CLR 131 SPECT/CT scans
Measure:Determination of event free survival following CLR 131 infusion in children, adolescents, and young adults
Time Frame:1 month to 5 years
Safety Issue:
Description:Time from first infusion of CLR 131 until progression or recurrence of disease
Measure:Determination of overall survival following CLR 131 infusion in children, adolescents, and young adults
Time Frame:1 month to 5 years
Safety Issue:
Description:Time from first infusion of CLR 131 until death due to any reason
Measure:Determine dosimetry of CLR 131 in children, adolescents, and young adults
Time Frame:up to 15 days post initial infusion
Safety Issue:
Description:Assessment of dosimetry via whole body planar imaging

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Cellectar Biosciences, Inc.

Trial 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

Last Updated

March 18, 2021