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

This study is currently recruiting participants.
Verified October 2016 by Cellectar Biosciences, Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02278315
First Posted: October 30, 2014
Last Update Posted: January 24, 2017
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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Cellectar Biosciences, Inc.
  Purpose
The primary objective of the study is to determine the safety and tolerability of I-131-CLR1404, 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.

Condition Intervention Phase
Multiple Myeloma Drug: I-131-CLR1404 Drug: dexamethasone Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase 1, Open-Label, Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Cellectar Biosciences, Inc.:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Other Outcome Measures:
  • 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


Estimated Enrollment: 33
Study Start Date: February 2015
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single
I-131-CLR1404 with or without concurrent dexamethasone
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

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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%; 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02278315


Locations
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States, 32224
Contact: Michele Maharaj    904-953-6136    maharaj.michele@mayo.edu   
Principal Investigator: Sikander Ailawadhi, MD         
United States, Illinois
Loyola University Medical Center Recruiting
Maywood, Illinois, United States, 60153
Contact: Palak Soni    708-327-3317    psoni1@luc.edu   
Principal Investigator: Patrick Stiff, M.D.         
United States, Wisconsin
University of Wisconsin Hospital and Clinics Recruiting
Madison, Wisconsin, United States, 53792
Contact: UW Cancer Connect    800-622-8922      
Principal Investigator: Natalie S Callander, MD         
Sponsors and Collaborators
Cellectar Biosciences, Inc.
Investigators
Principal Investigator: Natalie S Callander, MD University of Wisconsin, Madison
  More Information

Publications:
Responsible Party: Cellectar Biosciences, Inc.
ClinicalTrials.gov Identifier: NCT02278315     History of Changes
Other Study ID Numbers: DCL-14-002
First Submitted: October 22, 2014
First Posted: October 30, 2014
Last Update Posted: January 24, 2017
Last Verified: October 2016

Keywords provided by Cellectar Biosciences, Inc.:
Multiple Myeloma
Radiopharmaceutical
Therapy
Phase 1

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors