The primary objective of the study is to determine the safety and tolerability of I-131-CLR1404 as a single or multiple dose, with and without concurrent weekly dexamethasone, in patients with relapsed or refractory multiple myeloma who have previously been treated with, or are intolerant of, an immunomodulator and a proteasome inhibitor.
Multiple myeloma (MM) is an incurable, monoclonal proliferation of plasma cells. Approximately 80,000 Americans are affected by MM with approximately 22,000 new cases diagnosed and 11,000 deaths each year. The introduction of newer therapies in the past twenty years, such as autologous stem cell transplantation and novel agents such as proteasome inhibitors and immune modulating drugs has improved outcomes, with current median overall survival estimates of 3-10 years depending on a number of patient-, disease- and treatment-related factors. However, despite these innovations, myeloma relapse is inevitable. Therefore, there is a clear need for improved therapies for MM and, in particular, for relapsed disease. I-131-CLR1404 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). Radioiodinated CLR1404 has been evaluated in over 60 xenograft and spontaneous (transgenic) tumor models. In all but two cases of hepatocellular carcinoma, CLR1404 demonstrated selective cancer cell uptake and retention. In various rodent tumor models, I-131-CLR1404 has also demonstrated tumor growth delay and prolongation of survival. Based on the critical unmet medical need for effective agents with novel mechanisms of action in MM, the exquisite radiosensitivity of MM, and initial preclinical and clinical experience with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess I-131-CLR1404 in a MM-specific phase 1 trial.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
31
Single IV dose of I-131-CLR1404, increased/decreased by cohort
40 mg dexamethasone orally once weekly for up to 12 weeks
Multiple IV dose of I-131-CLR1404, increased/decreased by cohort
Mayo Clinic
Jacksonville, Florida, United States
Loyola University Medical Center
Maywood, Illinois, United States
Karmanos Cancer Institute
Detroit, Michigan, United States
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, United States
Number of participants with dose limiting toxicities (DLT)
DLT will be assessed by physical examination, vital signs, ECG, and laboratory values
Time frame: up to 85 days
Identification of recommended phase 2 dose of I-131-CLR1404 with concurrent weekly dexamethasone
Largest administered dose with concurrent weekly dexamethasone with at most a 17% dose limiting toxicity rate
Time frame: until non-tolerated dose is defined; dose escalation descision made upon review of data from a complete cohort (85 days after all subjects in cohort have received infusion)
Identification of recommended phase 2 dose of I-131-CLR1404 without dexamethasone
Largest administered dose without dexamethasone with at most a 17% dose limiting toxicity rate
Time frame: until non-tolerated dose is defined; dose escalation descision made upon review of data from a complete cohort (85 days after all subjects in cohort have received infusion)
Identify the recommended dosing schedule of I-131-CLR1404, in relapsed or refractory MM
Time frame: until non-tolerated dose is defined with both dosing regimens; dose escalation decision made upon review of data from a complete cohort (85 days after all subjects in cohort have received infusion)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.