- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02278315
Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma
Phase 1, Open-Label, Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma
Study Overview
Status
Conditions
Intervention / Treatment
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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Florida
-
Jacksonville, Florida, United States, 32224
- Mayo Clinic
-
-
Illinois
-
Maywood, Illinois, United States, 60153
- Loyola University Medical Center
-
-
Michigan
-
Detroit, Michigan, United States, 48201
- Karmanos Cancer Institute
-
-
Wisconsin
-
Madison, Wisconsin, United States, 53792
- University of Wisconsin Hospital and Clinics
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Single
I-131-CLR1404 with or without concurrent dexamethasone
|
Single IV dose of I-131-CLR1404, increased/decreased by cohort
Other Names:
40 mg dexamethasone orally once weekly for up to 12 weeks
Other Names:
Multiple IV dose of I-131-CLR1404, increased/decreased by cohort
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
up to 85 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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
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
|
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)
|
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)
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
through Day 85
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Natalie S Callander, MD, University of Wisconsin, Madison
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Cardiovascular Diseases
- Vascular Diseases
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Immunoproliferative Disorders
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Physiological Effects of Drugs
- Autonomic Agents
- Peripheral Nervous System Agents
- Anti-Inflammatory Agents
- Antineoplastic Agents
- Antiemetics
- Gastrointestinal Agents
- Glucocorticoids
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Antineoplastic Agents, Hormonal
- Dexamethasone
Other Study ID Numbers
- DCL-14-002
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Myeloma
-
Lawson Health Research InstituteThe Ottawa Hospital; Hamilton Health Sciences Corporation; Dalhousie University; Niagara Health SystemActive, not recruitingMultiple Myeloma in Relapse | Multiple Myeloma With Failed Remission | Multiple Myeloma Stage I | Multiple Myeloma Progression | Multiple Myeloma Stage II | Multiple Myeloma Stage IIICanada
-
National Cancer Institute (NCI)Active, not recruitingSmoldering Multiple Myeloma | Refractory Multiple Myeloma | DS Stage I Multiple Myeloma | DS Stage II Multiple Myeloma | DS Stage III Multiple MyelomaUnited States
-
Fred Hutchinson Cancer Research Center/University...National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Mayo ClinicCompletedMultiple Myeloma | Stage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
National Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
City of Hope Medical CenterCompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
University of WashingtonNational Cancer Institute (NCI)TerminatedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)CompletedStage I Multiple Myeloma | Stage II Multiple Myeloma | Stage III Multiple Myeloma | Refractory Multiple MyelomaUnited States
Clinical Trials on I-131-CLR1404
-
Cellectar Biosciences, Inc.Active, not recruitingOsteosarcoma | Ewing Sarcoma | Neuroblastoma | Rhabdomyosarcoma | Pediatric Brain Tumor | DIPG | Pediatric Solid Tumor | Pediatric LymphomaUnited States, Australia, Canada
-
Cellectar Biosciences, Inc.Withdrawn
-
University of Wisconsin, MadisonNational Institute of Dental and Craniofacial Research (NIDCR); Cellectar Biosciences...Active, not recruiting
-
Cellectar, IncCompletedSolid TumorsUnited States
-
Cellectar Biosciences, Inc.Completed
-
Cellectar Biosciences, Inc.RecruitingMultiple Myeloma | Waldenstrom Macroglobulinemia | Mantle Cell Lymphoma | Marginal Zone Lymphoma | Chronic Lymphocytic Leukemia | Lymphoplasmacytic Lymphoma | Diffuse Large B Cell Lymphoma | Small Lymphocytic Lymphoma | Central Nervous System LymphomaUnited States, Australia, Czechia, Greece, Israel, Brazil, Finland, France, Spain, Turkey, United Kingdom
-
Cellectar Biosciences, Inc.TerminatedGlioblastomaUnited States
-
Cellectar Biosciences, Inc.National Cancer Institute (NCI)RecruitingHigh-Grade GliomaUnited States, Canada
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Active, not recruitingRecurrent Thyroid Gland Carcinoma | Poorly Differentiated Thyroid Gland Carcinoma | Stage IV Thyroid Gland Follicular Carcinoma AJCC v7 | Stage IV Thyroid Gland Papillary Carcinoma AJCC v7 | Stage IVA Thyroid Gland Follicular Carcinoma AJCC v7 | Stage IVA Thyroid Gland Papillary Carcinoma AJCC... and other conditionsUnited States
-
University of WuerzburgDeutsche Krebshilfe e.V., Bonn (Germany)RecruitingDifferentiated Thyroid CarcinomaGermany