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Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02278315
Recruitment Status : Active, not recruiting
First Posted : October 30, 2014
Last Update Posted : April 9, 2020
Sponsor:
Information provided by (Responsible Party):
Cellectar Biosciences, Inc.

Tracking Information
First Submitted Date  ICMJE October 22, 2014
First Posted Date  ICMJE October 30, 2014
Last Update Posted Date April 9, 2020
Actual Study Start Date  ICMJE February 2015
Estimated Primary Completion Date April 15, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 27, 2014)
Number of participants with dose limiting toxicities (DLT) [ Time Frame: up to 85 days ]
DLT will be assessed by physical examination, vital signs, ECG, and laboratory values
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 15, 2018)
  • Identification of recommended phase 2 dose of I-131-CLR1404 with concurrent weekly dexamethasone [ 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) ]
    Largest administered dose with concurrent weekly dexamethasone with at most a 17% dose limiting toxicity rate
  • Identification of recommended phase 2 dose of I-131-CLR1404 without dexamethasone [ 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) ]
    Largest administered dose without dexamethasone with at most a 17% dose limiting toxicity rate
  • 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) ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 27, 2014)
  • Identification of recommended phase 2 dose of I-131-CLR1404 with concurrent weekly dexamethasone [ 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) ]
    Largest administered dose with concurrent weekly dexamethasone with at most a 17% dose limiting toxicity rate
  • Identification of recommended phase 2 dose of I-131-CLR1404 without dexamethasone [ 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) ]
    Largest administered dose without dexamethasone with at most a 17% dose limiting toxicity rate
Current Other Pre-specified Outcome Measures
 (submitted: October 27, 2014)
Determination of therapeutic activity of I-131-CLR1404 in relapsed or refractory multiple myeloma [ Time Frame: through Day 85 ]
Response assessment per International Uniform Response Criteria for Multiple Myeloma
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma
Official Title  ICMJE Phase 1, Open-Label, Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma
Brief Summary 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.
Detailed Description

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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: I-131-CLR1404
    Single IV dose of I-131-CLR1404, increased/decreased by cohort
    Other Names:
    • 131I-CLR1404
    • 18-(p-[I-131]-iodophenyl)octadecyl phosphocholine
    • CLR 131
  • Drug: dexamethasone
    40 mg dexamethasone orally once weekly for up to 12 weeks
    Other Name: Decadron
  • Drug: I-131-CLR1404
    Multiple IV dose of I-131-CLR1404, increased/decreased by cohort
    Other Names:
    • 131I-CLR1404
    • 18-(p-[I-131]-iodophenyl)octadecyl phosphocholine
    • CLR 131
Study Arms  ICMJE Experimental: Single
I-131-CLR1404 with or without concurrent dexamethasone
Interventions:
  • Drug: I-131-CLR1404
  • Drug: dexamethasone
  • Drug: I-131-CLR1404
Publications * Weichert JP, Clark PA, Kandela IK, Vaccaro AM, Clarke W, Longino MA, Pinchuk AN, Farhoud M, Swanson KI, Floberg JM, Grudzinski J, Titz B, Traynor AM, Chen HE, Hall LT, Pazoles CJ, Pickhardt PJ, Kuo JS. Alkylphosphocholine analogs for broad-spectrum cancer imaging and therapy. Sci Transl Med. 2014 Jun 11;6(240):240ra75. doi: 10.1126/scitranslmed.3007646.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: February 24, 2015)
33
Original Estimated Enrollment  ICMJE
 (submitted: October 27, 2014)
39
Estimated Study Completion Date  ICMJE April 15, 2020
Estimated Primary Completion Date April 15, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed multiple myeloma
  • Prior treatment with or intolerance to proteasome inhibitor and immunomodulator
  • Bone marrow biopsy within 28 days of study drug infusion demonstrating at least 5% plasma cell involvement
  • Progressive disease defined by any of following:

    25% increase in serum M-protein from lowest response value during (or after) last therapy and/or absolute increase in serum M-protein of > or equal to 0.5 g/dL; 25% increase in urine M-protein from lowest response value during (or after) last therapy and/or absolute increase in urine M-protein of > or equal to 200 mg/24h; 25% increase in bone marrow plasma cell percentage from lowest response value during (or after) last therapy - absolute bone marrow plasma cell percentage must be > or equal to 10% unless prior complete response when absolute bone marrow plasma cell percentage must be > or equal to 5%; 25% increase in serum FLC level from the lowest response value during (or after) last therapy - the absolute increase must be > 10 mg/dL; new onset hypercalcemia > 11.5 mg/dL

  • Measurable disease defined by any of following: Serum M-protein > 1 g/dL; Urine M-protein > 200 mg/24h; Serum free light chain (FLC) assay: involved FLC level > or equal to 10 mg/dL provided serum FLC ratio is abnormal; subjects who are non-secretors will be considered on a case-by-case basis
  • Eastern Cooperative Oncology Group performance status of 0 to 2
  • Life expectancy of at least 6 months
  • Have initiative and means to be compliant with protocol and within geographical proximity to make required study visits as judged by Investigator
  • Subject or legal representative has ability to read, understand and provide written informed consent for study related procedures
  • Women of childbearing potential must have negative pregnancy test within 24 hours of enrollment
  • Women of childbearing potential and men who are able to father a child, must agree to use an effective contraception method during study and for 12 months following study drug administration

Exclusion Criteria:

  • Grade 2 or greater toxicities due to previous therapies, subject to laboratory abnormalities listed below. Stable, tolerable Grade 2 adverse events may be allowed at discretion of Investigator
  • Prior external beam radiation therapy resulting in greater than 20% total bone marrow receiving greater than 20 Gy
  • Prior radioisotope therapy
  • Prior total body or hemi-body irradiation
  • Extradural tumor in contact with the spinal cord or tumor located where swelling in response to therapy may impinge upon spinal cord
  • Subject has any of following laboratory abnormalities: WBC < 3000/uL; ANC < 1500/uL; Hemoglobin < 8 g/dL; Estimated glomerular filtration rate < 30 mL/min/1.73 m2; ALT > 3 x ULN ; Bilirubin > 1.5 x ULN
  • Platelet count < 100,000/uL without full-dose anticogulation therapy
  • Platelet count < 150,000/uL with ongoing full-dose anticoagulation therapy
  • Clinically significant bleeding event, as judged by investigator, within prior 6 months
  • Chronic immunosuppressive therapy
  • Anti-platelet therapy, except low-dose aspirin for cardioprotection
  • PTT > 1.3 x ULN
  • INR > 1.3
  • Radiation therapy, chemotherapy, immunotherapy, investigational therapy or corticosteroid use within 2 weeks of or after eligibility-defining bone marrow biopsy. Bisphosphonates and denosumab are permitted if subject has been receiving for at least 90 days
  • History of hypersensitivity to iodine
  • Any other concomitant serious illness or organ system dysfunction in opinion of Investigator would either compromise subject safety or interfere with test drug safety evaluation
  • Major surgery within 6 weeks of enrollment
  • Known history of HIV, hepatitis C or hepatitis B infection
  • Pregnancy or breast-feeding
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02278315
Other Study ID Numbers  ICMJE DCL-14-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cellectar Biosciences, Inc.
Study Sponsor  ICMJE Cellectar Biosciences, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Natalie S Callander, MD University of Wisconsin, Madison
PRS Account Cellectar Biosciences, Inc.
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP