Multiple MyelomaPhase 1NCT02278315
Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma
A Phase 1 study testing I-131-CLR1404 and dexamethasone in people with Multiple Myeloma, run by Cellectar Biosciences, Inc. at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Myeloma
- What is being tested?
- I-131-CLR1404 and dexamethasone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 31 participants
- Where
- 4 sitesUnited States
- Study dates
- Feb 2015to 10 Aug 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Karmanos Cancer Institute
Detroit, Michigan, 48201
Mayo Clinic
Jacksonville, Florida, 32224
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792
Loyola University Medical Center
Maywood, Illinois, 60153
About this study
Official title: Phase 1, Open-Label, Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma
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.
Read the 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.
- Conditions
- Multiple Myeloma
- Being tested
- I-131-CLR1404, dexamethasone
- Keywords
- Multiple Myeloma, Radiopharmaceutical, Therapy, Phase 1
- Medical subject headings
- Multiple Myeloma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
I-131-CLR1404Drug
Also called 131I-CLR1404, 18-(p-[I-131]-iodophenyl)octadecyl phosphocholine, CLR 131
Single IV dose of I-131-CLR1404, increased/decreased by cohort
dexamethasoneDrug
Also called Decadron
40 mg dexamethasone orally once weekly for up to 12 weeks
I-131-CLR1404Drug
Also called 131I-CLR1404, 18-(p-[I-131]-iodophenyl)octadecyl phosphocholine, CLR 131
Multiple IV dose of I-131-CLR1404, increased/decreased by cohort
| Study group | Role | What they receive |
|---|---|---|
| Single | Experimental | I-131-CLR1404 with or without concurrent dexamethasone Receives: Drug: I-131-CLR1404; Drug: dexamethasone |
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, ECG, and laboratory values
Measured: up to 85 days
Secondary outcomes (3)
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
Measured: 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
Measured: 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
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Oct 2014 (estimated)
- Study startFeb 2015
- Primary completion9 Dec 2020
- Study completion10 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple MyelomaStudies 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
- 31 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cellectar Biosciences, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Natalie S Callander, MD, Principal investigator, University of Wisconsin, Madison
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02278315
- Sponsor's protocol ID
- DCL-14-002
- Status last verified
- Feb 2023
- First submitted
- 22 Oct 2014
- Last updated
- 22 Feb 2023
- Results posted
- No
- Data monitoring committee
- Yes
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.
PubMed 24920661
Study at a glance
From the registry record, last updated by the sponsor on 22 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Open-Label, Dose Escalation Study of I-131-CLR1404 in Patients With Relapsed or Refractory Multiple Myeloma
- ClinicalTrials.gov ID
- NCT02278315
- Acronym / sponsor ID
- DCL-14-002
- Conditions
- Multiple Myeloma
- Keywords
- Multiple Myeloma, Radiopharmaceutical, Therapy, Phase 1
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- Cellectar Biosciences, Inc.Industry (pharma, biotech, devices)
- Study start
- Feb 2015 (actual)
- Primary completion
- 9 Dec 2020 (actual)
- Study completion
- 10 Aug 2022 (actual)
- First posted
- 30 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Single | Experimental | Drug: I-131-CLR1404, Drug: dexamethasoneI-131-CLR1404 with or without concurrent dexamethasone |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| I-131-CLR1404Also: 131I-CLR1404, 18-(p-[I-131]-iodophenyl)octadecyl phosphocholine, CLR 131Single IV dose of I-131-CLR1404, increased/decreased by cohort | Drug | Single |
| dexamethasoneAlso: Decadron40 mg dexamethasone orally once weekly for up to 12 weeks | Drug | Single |
| I-131-CLR1404Also: 131I-CLR1404, 18-(p-[I-131]-iodophenyl)octadecyl phosphocholine, CLR 131Multiple IV dose of I-131-CLR1404, increased/decreased by cohort | Drug | Single |
Primary outcome
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
3 secondary outcomes
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)
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)
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)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Feb 2023.
- Background: PubMed 24920661Weichert 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Natalie S Callander, MD principal investigator
University of Wisconsin, Madison
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing I-131-CLR1404 and dexamethasone in people with Multiple Myeloma, run by Cellectar Biosciences, Inc. at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with dose limiting toxicities (DLT) (time frame: up to 85 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02278315, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Feb 2023.