Pediatric Solid TumorPhase 1CLOVER-2NCT03478462
Dose Escalation Study of CLR 131 in Pediatric Relapsed/Refractory Malignant Tumors Including Neuroblastoma and Sarcomas
A Phase 1 study testing CLR 131 in people with Pediatric Solid Tumor and Pediatric Lymphoma, run by Cellectar Biosciences, Inc. at 8 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 2 to 25 years
- Conditions the study is for
- Pediatric Solid Tumor, Pediatric Lymphoma, Pediatric Brain Tumor
- What is being tested?
- CLR 131
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 8 sitesin 3 countries
- Study dates
- 30 Apr 2019to Dec 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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
Show all 20Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 3 countries.
8 sites in 3 countries
United States6 sites
Duke University
Chapel Hill, North Carolina, 27708
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
Texas Children's Hospital
Houston, Texas, 77030
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Lucile Packard Children's Hospital
Palo Alto, California, 94304
Australia1 site
Children's Hospital at Westmead
Westmead, New South Wales, 2145
About this study
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
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.
Read the 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.
- Conditions
- Pediatric Solid Tumor, Pediatric Lymphoma, Pediatric Brain Tumor, DIPG, Neuroblastoma, Ewing Sarcoma
- Being tested
- CLR 131
- 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
- Medical subject headings
- Neuroblastoma, Sarcoma, Ewing, Rhabdomyosarcoma, Osteosarcoma, Medulloblastoma, Ependymoma, Glioma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CLR 131Drug
Also called I-131-CLR1404
IV dose of CLR 131, increased/decreased by dose level; single or fractionated dose
| Study group | Role | What they receive |
|---|---|---|
| CLR 131 | Experimental | CLR 131 intravenous administration Receives: Drug: CLR 131 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with dose limiting toxicities (DLT)
DLT will be assessed by physical examination, vital signs, and laboratory values
Measured: up to 64 days
Secondary outcomes (6)
Identification of recommended phase 2 dose of CLR 131 in children, adolescents, and young adults
Dose and regimen to be used in Phase 2 trials of CLR 131 in children, adolescents, and young adults
Measured: 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)
Determination of preliminary antitumor activity of CLR 131 in children, adolescents, and young adults
Response assessment per applicable criteria (e.g., Neuroblastoma Response Criteria (modified); RECIST 1.1; positron emission tomography response criteria in solid tumors (PERCIST); RANO)
Measured: through Day 85
Determination of therapeutic activity of CLR 131 in children, adolescents, and young adults
Assessment via 131-I/CLR 131 SPECT/CT scans
Measured: up to 22 days post initial infusion
Determination of event free survival following CLR 131 infusion in children, adolescents, and young adults
Time from first infusion of CLR 131 until progression or recurrence of disease
Measured: 1 month to 5 years
Determination of overall survival following CLR 131 infusion in children, adolescents, and young adults
Time from first infusion of CLR 131 until death due to any reason
Measured: 1 month to 5 years
Determine dosimetry of CLR 131 in children, adolescents, and young adults
Assessment of dosimetry via whole body planar imaging
Measured: up to 15 days post initial infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2018
- Study start30 Apr 2019
- Primary completion30 Jun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pediatric Solid TumorStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Cellectar Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Jarrod Longcor, Study director, Cellectar Biosciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03478462
- Sponsor's protocol ID
- DCL-17-001
- Acronym
- CLOVER-2
- Status last verified
- Sep 2026
- First submitted
- 20 Mar 2018
- Last updated
- 1 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No