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

NCT07766421 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: DCL-26-0012026-527281-78-00
• Study Type: interventional
• Target: 219
• Locations: 0 countries
• Sites: N/A

Brief 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 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.

Conditions

Waldenstrom Macroglobulinaemia; Waldenstrom Macroglobulinemia; Waldenstrom's Macroglobulinaemia Refractory; Waldenstrom Macroglobulinemia With Nodal Disease; Waldenstrom's Macroglobulinemia Recurrent

Keywords

iopofosine I 131; CLR 131; waldenstroms

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (4)

• Major response rate (MRR)

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

• Overall response rate (ORR)

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

• VGPR/CR rates

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

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

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

Other Outcomes (2)

• Overall survival (OS)

  From randomization until death from any cause or study closure (5 years after last patient first dose).

• Duration of response (DOR)

  Time from the first documentation of response to the subsequent date of the first occurrence of PD or death due to any reason, or until study closure (5 years after last patient first dose).

Study Arms (2)

Iopofosine I 131

EXPERIMENTAL

Iopofosine I 131

Drug: Iopofosine I 131

R-CD

ACTIVE COMPARATOR

Rituximab, cyclophosphamide, dexamethasone

Drug: Rituximab (active comparator); Drug: Cyclophosphamate; Drug: Dexamethasone

Interventions

Iopofosine I 131 DRUG

Fractionated dose

Also known as: CLR 131

Iopofosine I 131

Rituximab (active comparator) DRUG

Rituximab

R-CD

Cyclophosphamate DRUG

Cyclophosphamide

R-CD

Dexamethasone DRUG

Dexamethasone

R-CD

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Cellectar Biosciences, Inc.: lead

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

CLR1404; Rituximab; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Central Study Contacts

Kate Oliver

CONTACT

608-441-8120; clinical@cellectar.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 30, 2026
• First Posted: August 14, 2026
• Study Start (Estimated): December 1, 2026
• Primary Completion (Estimated): January 1, 2032
• Study Completion (Estimated): January 1, 2035
• Last Updated: August 14, 2026

Record last verified: 2026-08