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Waldenstrom MacroglobulinaemiaPhase 3NCT07766421

Evaluation of Iopofosine I 131 vs. R-CD in WM Patients

A Phase 3 study testing Iopofosine I 131, Rituximab (active comparator) and Cyclophosphamate in people with Waldenstrom Macroglobulinaemia and Waldenstrom Macroglobulinemia, run by Cellectar Biosciences, Inc..

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Iopofosine I 131, Rituximab (active comparator) and Cyclophosphamate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
219 participants
Where
No sites listed yet
Study dates
Dec 2026to Jan 2035
Phase
Phase 3
Are there results?
Not yet: the study is under way

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 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:
  • 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.
  • 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.).
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

Kate Oliver contact

608-441-8120

clinical@cellectar.com

About this study

Official title: 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

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.
Read more

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.
Read the detailed description

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.

Being tested
Iopofosine I 131, Rituximab (active comparator), Cyclophosphamate, Dexamethasone
Keywords
iopofosine I 131, CLR 131, waldenstroms
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Iopofosine I 131Drug

    Also called CLR 131

    Fractionated dose

  • Rituximab (active comparator)Drug

    Rituximab

  • CyclophosphamateDrug

    Cyclophosphamide

  • DexamethasoneDrug

    Dexamethasone

Study groups in NCT07766421
Study groupRoleWhat they receive
Iopofosine I 131ExperimentalIopofosine I 131
Receives: Drug: Iopofosine I 131
R-CDActive comparatorRituximab, cyclophosphamide, dexamethasone
Receives: Drug: Rituximab (active comparator); Drug: Cyclophosphamate; Drug: Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Superiority of progression free survival (PFS)

    A survival analysis will be performed comparing treatment arms using the Cox Proportional Hazard model to determine the hazard ratio, corresponding 95% CI, and p-value to determine superiority between iopofosine I 131 and R-CD.

    Measured: From baseline randomization through study completion of progressive disease, or death due to any reason (whichever status is recorded first).

Secondary outcomes (4)

  1. Major response rate (MRR)

    Proportion of participants with CR, VGPR, or PR determined from the modified IWWM-11 response criteria. Corresponding 95% CO using the Clopper-Pearson method will be reported.

    Measured: Day 1 of Cycle 1 of dosing through the start of new antineoplastic treatment or early termination, whichever occurs first.

  2. Overall response rate (ORR)

    Proportion of participants with CR, VGPR, PR, or MR determined from the modified IWWM-11 response criteria. Corresponding 95% CO using the Clopper-Pearson method will be reported.

    Measured: Day 1 of Cycle 1 of dosing until start of new antineoplastic treatment or early termination, whichever occurs first.

  3. VGPR/CR rates

    Proportion of participants with VGPR or CR determined from the modified IWWM-11 response criteria. The corresponding 95% CI using the Clopper-Pearson method will be reported for each treatment group

    Measured: Day 1 of Cycle 1 of dosing until the start of new antineoplastic treatment or early termination, whichever occurs first.

  4. Number of adverse events related to trial medications (iopofosine I 131 or R-CD)

    Adverse events are graded per NCI CTCAE v5.0

    Measured: Assessed throughout the study through 1 year following completion of treatment.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2026
  2. Study startDec 2026 (estimated)
  3. Primary completionJan 2032 (estimated)
  4. Study completionJan 2035 (estimated)

Resources

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 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
219 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07766421
Sponsor's protocol ID
DCL-26-001
Other IDs
2026-527281-78-00
Status last verified
Aug 2026
First submitted
30 Jul 2026
Last updated
14 Aug 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Iopofosine I 131, Rituximab (active comparator) and Cyclophosphamate in people with Waldenstrom Macroglobulinaemia and Waldenstrom Macroglobulinemia, run by Cellectar Biosciences, Inc..

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 22 inclusion and 30 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: opening soon, as of the sponsor's last update on 14 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kate Oliver (608-441-8120, clinical@cellectar.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Superiority of progression free survival (PFS) (time frame: From baseline randomization through study completion of progressive disease, or death due to any reason (whichever status is recorded first).). 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 NCT07766421.

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 14 Aug 2026.

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