# An Open-Label, Multicenter, Phase 2/3 Efficacy and Safety Study of a targeted radiotherapy in Patients with Relapsed or Refractory Waldenstroms Macroglobulinemia

> **NIH NIH R44** · CELLECTAR BIOSCIENCES, INC. · 2022 · $755,603

## Abstract

ABSTRACT
Waldenstrom’s Macroglobulinemia (WM) is an incurable and life-threatening malignant tumor. It is a rare and
chronic form of B-cell non-Hodgkin lymphoma (NHL), characterized by small B lymphocytes, plasmacytoid
lymphocytes, and plasma cells typically involving the bone marrow, lymph nodes, and organs such as spleen
and liver. Patients also have detectable levels of monoclonal immunoglobulin (Ig) M gammopathy with bone
marrow involvement. The median survival of WM patients from the time of diagnosis is approximately 6 years,
depending on prognostic indicators. The main causes of death include disease progression, transformation to
high-grade lymphoma or therapeutic complications. While many drugs are utilized, there is no standard treatment
in first-line WM patients. Recommendations include using chemoimmunotherapy with rituximab (anti-CD20
monoclonal antibodies) or the combination of rituximab with proteasome inhibitors as well as ibrutinib for some
patients. Because all patients’ disease eventually progresses, and ibrutinib is the only approved second line
therapy, there continues to be a significant unmet medical need in patients in the relapsed or refractory setting.
We propose the clinical development of CLR 131 for the treatment of relapsed WM in patients who do not
respond to ibrutinib (or other Bruton’s tyrosine kinase inhibitors) or are intolerant to it. CLR 131, a tumor targeted
radiotherapeutic with a phospholipid ether (PLE) core, is expected to have an enhanced efficacy and safety
profile and provide durable efficacy due to CLR 131 actually modifying the disease, regardless of the underlying
genetic landscape of WM. CLR 131 exploits the tumor-targeting properties of PLEs to provide a targeted delivery
of radiation to malignant tumor cells and minimizes radiation exposure to normal tissues. PLEs selectively insert
into lipid rafts, which are enriched on the surface of tumor cells, and use them as a gateway for cellular entry.
The combined nonclinical data confirm that administration with CLR 131 results in inhibition of tumour growth
and increased survival. More importantly, preliminary data from 6 WM subjects participating in our Phase II open-
label, multi-center, study of CLR 131 in patients with relapsed or refractory select types of B-cell malignancies,
showed an overall response rate of 100%, with one patient with a complete response, four patients with a partial
response, one patient with a minimal response showing a 45% reduction in IgM (50% reduction equates to a
partial response). In this project. we will conduct a non-randomized open-label, multi-center, Phase II/III efficacy
and safety study of intravenous administration of CLR 131 in at least 50 patients with WM who have failed
standard of care first line treatment and either failed or had a suboptimal response to any BTK inhibitors (i.e.,
ibrutinib, zanubrutinib or acalabrutinib). This study will allow us to receive regulatory approval for CLR 131 in the
examined ...

## Key facts

- **NIH application ID:** 10477049
- **Project number:** 5R44CA265558-02
- **Recipient organization:** CELLECTAR BIOSCIENCES, INC.
- **Principal Investigator:** Jarrod Longcor
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $755,603
- **Award type:** 5
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10477049

## Citation

> US National Institutes of Health, RePORTER application 10477049, An Open-Label, Multicenter, Phase 2/3 Efficacy and Safety Study of a targeted radiotherapy in Patients with Relapsed or Refractory Waldenstroms Macroglobulinemia (5R44CA265558-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10477049. Licensed CC0.

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