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.
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.
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.
