ClinicalTrials.gov record NCT07766421
Evaluation of Iopofosine I 131 vs. R-CD in WM Patients
An Open-Label, Multicenter, Randomized, Phase 3 Trial of Iopofosine I 131 Versus Rituximab-Cyclophosphamide-Dexamethasone (R-CD) in Waldenstrom Macroglobulinemia Patients Previously Treated With a Bruton Tyrosine Kinase Inhibitor
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This Phase 3 randomized, open-label trial compares iopofosine I 131 with Rituximab‑Cyclophosphamide‑Dexamethasone (R‑CD) in people with Waldenstrom Macroglobulinemia previously treated with a Bruton tyrosine kinase inhibitor. Participants are assigned to one of two drug arms and followed to measure progression-free survival, response rates, and safety. The study is unmasked and uses parallel treatment groups.
What it is studying. The study is testing iopofosine I 131 against R‑CD to see which treatment is associated with longer progression-free survival in people with Waldenstrom Macroglobulinemia who previously received a BTK inhibitor. It will also compare antitumor activity using major response rate, overall response rate, and rates of very good partial response (VGPR) and complete response (CR). Adverse events related to the study medications will be recorded. Up to 219 evaluable patients will be enrolled.
What the researchers hope to learn. Determine whether iopofosine I 131 is superior to R‑CD for progression-free survival in this patient group; assess antitumor activity by major response rate, overall response rate, and VGPR/CR rates; and collect safety data on adverse events related to the trial medications.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
The goal of this clinical trial is to evaluate whether iopofosine I 131 is more effective than the combination Rituximab-Cyclophosphamide-Dexamethasone (R-CD). The main question the study aims to answer is:
- Does iopofosine I 131 work better than R-CD when looking at the length of time during and after the treatment that a patient lives with WM but it does not get worse.
Participants will:
- Be randomly assigned to received either iopofosine I 131 or R-CD.
- If assigned to iopofosine I 131, have it administered via infusion 2 times each cycle for a total of 2 cycles (each cycle is about 3 months long).
- If assigned to R-CD, it will be administered for up to six cycles, and each cycle is 3-weeks long
- Visit the clinic once every 3 weeks for checkups and testing.
- Report any side effects or new medications.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Iopofosine I 131
- Rituximab (active comparator)
- Cyclophosphamate
- Dexamethasone
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Histologically and serologically confirmed diagnosis of WM.
- Received at least one prior therapy for WM.
- Received treatment with a BTKi (including covalent BTKi or non-covalent BTKi).
- Symptomatic disease progression requiring therapy. Specifically, participant must meet one of the following:
- a. Biochemical progression or progression by imaging: i. ≥ 25% increase in serum IgM levels with a minimum increase of 500 mg/dL from nadir. If serum IgM is used to support progression, 2 sequential measurements are required. ii. Any new lesion (>1.5 cm in any axis) or unequivocal evidence of an increase by >50% in any axis to >1.5 cm in size of previously involved extramedullary disease sites from their nadir measurements. Progression by imaging does not require re-confirmation for eligibility.
- b. Clinical signs or symptoms as determined by the investigator (e.g., constitutional symptoms (fatigue, fevers, night sweats, etc.), hyperviscosity syndrome, demyelinating peripheral neuropathy, cytopenias, organomegaly, etc.).
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
- Participant is ≥ 18 years of age.
- Life expectancy ≥ 6 months.
- Presence of elevated total serum IgM (2x above institutional upper limit of normal (ULN)). Participants with extramedullary disease only may not be enrolled.
- Participant must meet the following hematological laboratory criteria:
- Platelets ≥ 75,000/uL.
- Absolute neutrophil count (ANC) ≥ 1000/uL
- Hemoglobin ≥ 8 g/dL, that can be maintained by packed red blood cell (PRBC) transfusions
- Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2 (as calculated using the CKD-EPI 2021 formula) OR serum creatinine ≤ 1.5 x ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 × ULN
- Bilirubin < 1.5 × ULN, except for patients with Gilbert's syndrome, who may be enrolled if bilirubin is < 3 x ULN or direct bilirubin is < 1.5 x ULN.
- Patient who has undergone autologous stem cell transplant must be at least one year from the date of hematopoietic recovery.
- Patient must express willingness and ability to comply with scheduled study visits, treatment plans, laboratory tests, and other study procedures.
- Patient or their legally authorized representative must have the ability to understand and provide signed informed written consent before the initiation of any study-related procedures.
- Female patients of childbearing potential, defined as all women physiologically capable of becoming pregnant, must have a negative serum or urine beta human chorionic gonadotropin (b-hCG) pregnancy test result within one week prior to first dose of study treatment and agree to use a highly effective method of contraception during the study and for 12 months following administration of the last dose of study treatment.
- Sexually active males, including those who have had a vasectomy, must agree to use a condom during intercourse while receiving iopofosine I 131 or R-CD and for three months after the last dose of iopofosine I 131 or R-CD.
Exclusion criteria
- Receipt of:
- Anti CD-20 MoAb < 6 months prior to study drug administration.
- Any conventional cytotoxic chemotherapy ≤ four weeks prior to study drug administration.
- Non-anti CD20 MoAb therapy for the treatment of WM ≤ three months prior to study drug administration. i. The only exception to this is for those patients who have documented evidence of progression while receiving non-anti CD20 MoAb therapy.
- BTKi therapy ≤ 48 hours prior to study drug administration.
- Any investigational agents ≤ two weeks or five half-lives, whichever is shorter, prior to study drug administration.
- Evidence of Bing Neel disease or disease transformation at the time of study entry.
- Evidence of or suspected of having Myelodysplastic Syndrome (MDS) based upon laboratory and bone marrow testing at the time of trial entry. Note: this includes suspicion of or presence of MDS or CHIP mutation as per the trial screening bone marrow biopsy.
- Ongoing Grade 2 or greater toxicities due to previous therapies, excluding alopecia, that in the opinion of the investigator might be exacerbated by study treatment.
- Prior external-beam radiation therapy resulting in greater than 20% of total bone marrow receiving greater than 20 Gy. For estimation purposes, the following bone marrow percentages can be used:
- Vertebral bodies: Cervical 0.5%, thoracic 1%, lumbar 2% per vertebral body
- Hemipelvis (ilium, acetabulum, ischium): 13% per side
- Sacrum: 10%
- Skull: 12%
- Scapula: 5% per side
- Ribs: 4% per side
- Femur: 3% per side
- Prior total body irradiation.
- Patients with presence of second malignancies in addition to WM. However, patients with the following malignancies within the past two years may enroll as long as there is no evidence of disease: non-melanoma skin cancers only requiring topical treatment or surgical excision; melanoma in situ; localized cancer of the prostate with current prostate-specific antigen of < 0.1 µg/mL; treated cervical carcinoma in situ; or ductal/lobular carcinoma in situ of the breast.
- Ongoing chronic immunosuppressive therapy.
- Any other concomitant serious illness or organ system dysfunction (including cardiac and pulmonary dysfunction) that in the opinion of the Investigator would either compromise patient safety or interfere with the evaluation of the safety of the study drug.
- Major surgery (e.g., intra-abdominal, intra-thoracic, or intra-pelvic) ≤ 4 weeks prior to study drug administration, or lack of recovery from side effects of such surgery. Video-assisted thoracic surgery (VATS) and mediastinoscopy, placement of central venous catheter, endoscopy procedures, and percutaneous tissue biopsies will not be considered major surgery and patients can receive study drug ≥ one week after these procedures.
- History of hypersensitivity to thyroid protection medication (e.g., potassium iodide, Lugol's solution, etc.), murine compounds, or anti CD-20 MoAbs (e.g., rituximab).
- History of severe hypersensitivity reactions to cyclophosphamide, any of its metabolites, or to other components of the product.
- History of hypersensitivity to any components of dexamethasone, including sodium sulfites.
- Ongoing urinary outflow obstruction or systemic fungal infection.
- Known history of human immunodeficiency virus (HIV).
- Known history or active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) defined by positive polymerase chain reaction (PCR). Hepatitis patients receiving antiviral therapy (e.g., entecavir) who do not have a positive PCR are eligible.
- Presence of active infection within 72 hours prior to initiation of study treatment. Patients with ongoing use of prophylactic antibiotics, antifungals, or antivirals are eligible as long as there is no evidence of active infection and the antibiotics, antifungals, or antivirals are not included on the list of prohibited medications.
- Pregnancy or breast-feeding.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
This study designed to demonstrate superiority of progression free survival (PFS) of iopofosine I 131 in comparison to Rituximab-Cyclophosphamide-Dexamethasone (R-CD) in patients with WM who are relapsed or refractory to a Bruton tyrosine kinase inhibitor (BTKi). It will also determine the antitumor activity of iopofosine I 131 as compared to R-CD through assessment of major response rate, overall response rate, and rates of very good partial response and complete response. Up to 219 evaluable patients will be enrolled.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants are randomly assigned to one of two treatment groups. One group receives iopofosine I 131 by infusion twice each cycle for a total of 2 cycles (each cycle is about 3 months long); the other group receives rituximab with cyclophosphamide and dexamethasone (R‑CD) for up to six cycles, each 3 weeks long. You will visit the clinic about every 3 weeks for checkups and testing, and you will be asked to report side effects or any new medications. Adverse events and disease status will be monitored during the study and adverse events will be recorded for one year after treatment ends.
How the study is structured. Phase 3 interventional trial with random assignment to two parallel, open-label arms (no masking). Arm 1: iopofosine I 131 given as fractionated doses (two infusions each cycle for a total of two cycles; each cycle ~3 months). Arm 2: R‑CD (rituximab, cyclophosphamide, dexamethasone) given for up to six cycles, each cycle 3 weeks. The primary outcome is progression-free survival; responses and adverse events are secondary outcomes.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry says recruitment has not started. When is it expected to open, and can I register interest now?
- No sites are listed on the registry yet. Where will the study take place?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Waldenström macroglobulinemia
Important dates
- Study start
- December 2026 (estimated)
- Primary completion
- January 2032 (estimated)
- Study completion
- January 2035 (estimated)
- Target enrollment
- 219 participants (estimated)
- Last updated on registry
- Aug 14, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Cellectar Biosciences, Inc.
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Kate Oliver 📞 608-441-8120 ✉ clinical@cellectar.com
Participating sites
Study locations have not been posted on ClinicalTrials.gov yet. This study is not yet recruiting, so sites may be added when recruitment begins. The central study contact above may be able to tell you about planned sites.
Terms used on this page · explanations by MedicalUpdates.ai
- randomly assigned
- Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
- prior therapy
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- ECOG
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- Life expectancy
- Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- Absolute neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- Estimated glomerular filtration rate
- A blood-test estimate of how well the kidneys are filtering. Lower numbers mean reduced kidney function; many studies set a minimum value.
- autologous stem cell transplant
- A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
- legally authorized representative
- A person who is legally allowed to make decisions, including consent to research, on behalf of someone who cannot consent for themselves.
- childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- study drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- five half-lives
- The time it takes for the amount of a drug in the body to fall by half. 'Five half-lives' is often used as the point at which a previous drug has essentially left the body.
- biopsy
- Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
- immunosuppressive
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- prohibited medications
- A medicine that participants may not use during the study, usually because it could interfere with the study treatment or its measurement.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- superiority
- What a comparison is designed to show. A superiority study asks whether the new treatment is better than the comparator; a non-inferiority study asks whether it is not meaningfully worse.
- progression free survival
- The length of time during and after treatment that a person lives without the condition getting worse, as defined by the study.
- relapsed or refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- very good partial response
- A response category used in some blood conditions meaning the disease marker has fallen a great deal but not disappeared. The exact definition depends on the condition and the study.
- complete response
- No sign of the condition can be found with the tests used in the study. It does not always mean the condition is gone permanently, and the definition depends on the condition and the study.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this website; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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