Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia

NCT ID: NCT02952508

Last Updated: 2025-03-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-26

Study Completion Date

2026-12-22

Brief Summary

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Part A of this study evaluates iopofosine I 131 (CLR 131) in patients with select B-cell malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and central nervous system lymphoma (CNSL) who have been previously treated with standard therapy for their underlying malignancy. Part B (CLOVER-WaM) is a pivotal efficacy study evaluating IV administration of iopofosine I 131 in patients with WM that have received at least two prior lines of therapy.

Detailed Description

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B-cell malignancies represent a diverse collection of diseases and, taken together, make up the majority of hematologic malignancies. B-cell lymphomas represent the largest percentage of these neoplasms, and the relapsed and/or refractory B-cell lymphomas have proven very difficult to treat. Patients that have failed prior therapy, including WM patients, represent a very challenging patient population with significantly reduced life-expectancy.

Iopofosine I 131 is a targeted radiotherapeutic that exploits the selective uptake and retention of Cellectar's proprietary phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound is radiolabeled with the radioisotope iodine-131 (I-131) which has previously been used approved for use in select tumors. Iopofosine I 131 has been evaluated in over 80 xenograft and spontaneous (transgenic) tumor models where it was demonstrated to be effective in eliminating tumors.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in B-cell malignancies, Cellectar Biosciences has chosen to expand this ongoing study to assess iopofosine I 131 in a pivotal expansion cohort in Waldenstrom's Macroglobulinemia patients that have received at least two prior lines of therapy.

Conditions

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Waldenstrom Macroglobulinemia Multiple Myeloma Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Lymphoplasmacytic Lymphoma Marginal Zone Lymphoma Mantle Cell Lymphoma Diffuse Large B Cell Lymphoma Central Nervous System Lymphoma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Iopofosine I 131, intravenous administration WM

Iopofosine I 131 in Waldenstroms Macroglobulinemia

Group Type EXPERIMENTAL

Iopofosine I 131 single dose

Intervention Type DRUG

Radiopharmaceutical

Iopofosine I 131 multiple dose

Intervention Type DRUG

Radiopharmaceutical

Iopofosine I 131 fractionated dose

Intervention Type DRUG

Radiopharmaceutical

Iopofosine I 131, intravenous administration MM

Iopofosine I 131 in Multiple Myeloma

Group Type EXPERIMENTAL

Iopofosine I 131 single dose

Intervention Type DRUG

Radiopharmaceutical

Iopofosine I 131 multiple dose

Intervention Type DRUG

Radiopharmaceutical

Iopofosine I 131 fractionated dose

Intervention Type DRUG

Radiopharmaceutical

Iopofosine I 131, intravenous administration CNS Lymphoma

Iopofosine I 131 in Central Nervous System Lymphoma

Group Type EXPERIMENTAL

Iopofosine I 131 fractionated dose

Intervention Type DRUG

Radiopharmaceutical

Iopofosine I 131 intravenous administration NHL [CLOSED]

Iopofosine I 131 in Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, and Diffuse Large B-Cell Lymphoma

Group Type EXPERIMENTAL

Iopofosine I 131 single dose

Intervention Type DRUG

Radiopharmaceutical

Iopofosine I 131 multiple dose

Intervention Type DRUG

Radiopharmaceutical

Iopofosine I 131 fractionated dose

Intervention Type DRUG

Radiopharmaceutical

Interventions

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Iopofosine I 131 single dose

Radiopharmaceutical

Intervention Type DRUG

Iopofosine I 131 multiple dose

Radiopharmaceutical

Intervention Type DRUG

Iopofosine I 131 fractionated dose

Radiopharmaceutical

Intervention Type DRUG

Other Intervention Names

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I-131-CLR1404 CLR 131 I-131-CLR1404 CLR 131 I-131-CLR1404 CLR 131

Eligibility Criteria

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Inclusion Criteria

* Histologically or cytologically confirmed MM; Patients with primary or secondary CNSL may be enrolled.
* ECOG performance status of 0 to 2
* 18 years of age or older
* Life expectancy of at least 6 months
* Platelets ≥ 75,000/µL (if full-dose anticoagulation therapy is used, platelets ≥ 100,000/µL are required)
* WBC count ≥ 3000/µL
* Absolute neutrophil count ≥ 1500/µL
* Hemoglobin ≥ 9 g/dL (last transfusion, if any, must be at least 1 week prior to study registration, and no transfusions are allowed between registration and dosing)
* Estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2
* Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN)
* Bilirubin \< 1.5 × ULN
* International normalized ratio (INR) \< 2.5
* If patient is on full-dose anticoagulation therapy, the anticoagulation therapy must be reversible and reversal of the anticoagulation therapy must not be life-threatening, as judged by the Investigator
* Patients who have undergone stem cell transplant must be at least 100 days from transplant

Patients with Multiple Myeloma

* At least 5 prior regimens, which must include at least 1 approved proteasome inhibitor (bortezomib, carfilzomib, or ixazomib), at least 1 approved immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide), and at least 1 approved monoclonal antibody (e.g., daratumumab or elotuzumab) with or without maintenance therapy, unless patients are intolerable to such agents or ineligible to receive such agents.
* At least triple-class refractory (refractory to a proteasome inhibitor, immunomodulatory agent, and a monoclonal antibody)
* Progressive disease defined by any of the following:

* 25% increase in serum M-protein from the lowest response value during (or after) last therapy and/or absolute increase in serum M-protein of ≥ 0.5 g/dL
* 25% increase in urine M-protein from the lowest response value during (or after) last therapy and/or absolute increase in urine M-protein of ≥ 200 mg/24 h
* 25% increase in bone marrow plasma cell percentage from the lowest response value during (or after) last therapy. Absolute bone marrow plasma cell percentage must be ≥ 10% unless prior CR when absolute bone marrow plasma cell percentage must be ≥ 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
* Failure to obtain a partial response or better to current treatment, or cannot further improve their response to current treatment
* Appearance of new extramedullary disease
* Measurable disease defined by any of the following:

* Serum M-protein \> 0.5 g/dL
* Urine M-protein \> 200 mg/24 h
* Serum FLC assay: Involved FLC level ≥ 10 mg/dL provided serum FLC ratio is abnormal.

\[CLOSED\] Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma/Waldenstom Macroglobulinemia, or Marginal Zone Lymphoma

* Prior treatment with at least 2 prior regimens, which may include chemotherapy, an approved anti-CD20 antibody with or without maintenance therapy, and an approved targeted agent, unless patients are ineligible to receive such agents
* Patients with Helicobacter pylori+ mucosa-associated lymphoid tissue lymphoma must have received 1 prior antibiotic regimen for H pylori
* At least 1 measurable nodal lesion with longest diameter \> 15 mm or 1 measurable extranodal lesion (eg, hepatic nodule) with longest diameter \> 10 mm. Additional parameters (e.g., measurable IgM for patients with Lymphoplasmacytic Lymphoma) may be allowed if they meet current NCCN guidelines for symptomatic disease. Patients with uptake by FDG-PET scan may be allowed with prior approval of Sponsor.

\[CLOSED\] Patients with Mantle Cell Lymphoma

* Prior treatment with at least 1 prior regimen
* At least 1 measurable nodal lesion with longest diameter \> 15 mm or 1 measurable extranodal lesion (eg, hepatic nodule) with longest diameter \> 10 mm. Patients with uptake by FDG-PET scan may be allowed with prior approval of Sponsor.

\[CLOSED\] Patients with Diffuse Large B-Cell Lymphoma

* Relapsed or refractory to combination chemotherapy for DLBCL that contains rituximab and an anthracycline; or is intolerable to such agents. Relapsed disease is defined as either recurrence of disease after a CR or PD after achieving a partial response (PR) or SD. Refractory disease is defined as failure to achieve at least SD with any 1 line of therapy or with PD ≤ 3 months of the most recent chemotherapy regimen.
* At least 1 measurable nodal lesion with longest diameter \> 15 mm or 1 measurable extranodal lesion (eg, hepatic nodule) with longest diameter \> 10 mm. Patients with uptake by FDG-PET scan may be allowed with prior approval of Sponsor.

Patients with CNS Lymphoma

* Must have biopsy-proven disease and must have received at least one prior intervention for their disease.
* Must be at least two weeks from CNS biopsy before administration of iopofosine I 131.
* Must have at least one lesion with enhancement on brain imaging.
* Stable (or decreasing) dose of corticosteroids or anti-convulsant medication for at least 7 days prior to dosing


* Histologically or cytologically confirmed WM. Patients with a diagnosis of LPL may be enrolled with prior Sponsor approval.
* Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 (Appendix C)
* Patient is 18 years of age or older
* Life expectancy of at least 6 months
* Received at least two prior lines of therapy for WM
* Measurable IgM (above upper limit of normal) OR at least one measurable nodal lesion with longest diameter \> 15 mm or one measurable extranodal lesion (e.g., hepatic nodule) with longest diameter \> 10 mm

Exclusion Criteria

* Ongoing Grade 2 or greater toxicities due to previous therapies. Stable, tolerable Grade 2 AEs (eg, neuropathy) may be allowed.
* Prior external-beam RT resulting in greater than 20% of total bone marrow receiving greater than 20 Gy.
* Prior total body or hemi-body irradiation. Patients who have received prior low-dose total body or hemi-body irradiation may be allowed on a case-by-case basis after discussion with Sponsor (considerations may include factors such as time since irradiation, total lifetime accumulated dose, etc.)
* Extradural tumor in contact with the spinal cord or tumor located where swelling in response to therapy may impinge upon the spinal cord
* For patients with CLL/SLL, LPL, or MZL, transformation to a more aggressive form of NHL
* Ongoing chronic immunosuppressive therapy
* Clinically significant bleeding event within prior 6 months
* Ongoing anti-platelet therapy (except low-dose aspirin \[eg, 81 mg daily\] for cardioprotection)
* Anti-cancer therapy within two weeks of initial iopofosine I 131 infusion. Low dose dexamethasone for symptom management is allowed
* Radiation therapy, chemotherapy, immunotherapy, or investigational therapy within 2 weeks of eligibility-defining bone marrow biopsy.
* For patients with primary or secondary CNSL, active bleeding in the tumor bed and/or uncontrolled seizure activity


* Ongoing Grade 2 or greater toxicities due to previous therapies, excluding alopecia.
* Prior external-beam RT resulting in greater than 20% of total bone marrow receiving greater than 20 Gy.
* Prior total body or hemi-body irradiation. Patients who have received prior low-dose total body or hemi-body irradiation may be allowed on a case-by-case basis after discussion with Sponsor (considerations may include factors such as time since irradiation, total lifetime accumulated dose, etc.)
* Patients with second malignancies in addition to WM, if the second malignancy has required therapy in the last 2 years or is not in remission; exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy
* Anti-cancer therapy within two weeks of initial iopofosine I 131 infusion.
* Need for acute treatment of WM (e.g., those with hyperviscosity)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cellectar Biosciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jarrod Longcor

Role: STUDY_DIRECTOR

Cellectar Biosciences

Locations

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Cellectar Biosciences site

Los Angeles, California, United States

Site Status

Cellectar Biosciences site

Redlands, California, United States

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Cellectar Biosciences site

Washington D.C., District of Columbia, United States

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Cellectar Biosciences site

Jacksonville, Florida, United States

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Cellectar Biosciences site

Miami, Florida, United States

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Cellectar Biosciences site

Tampa, Florida, United States

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Cellectar Biosciences

Atlanta, Georgia, United States

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Cellectar Biosciences site

Maywood, Illinois, United States

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Cellectar Biosciences site

Warrenville, Illinois, United States

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Cellectar Biosciences site

Westwood, Kansas, United States

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Cellectar Biosciences site

New Orleans, Louisiana, United States

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Cellectar Biosciences site

Baltimore, Maryland, United States

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Cellectar Biosciences

Bethesda, Maryland, United States

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Cellectar Biosciences site

Boston, Massachusetts, United States

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Cellectar Biosciences

North Bergen, New Jersey, United States

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Cellectar Biosciences site

Buffalo, New York, United States

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Cellectar Biosciences site

New York, New York, United States

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Cellectar Biosciences site

Rochester, New York, United States

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Cellectar Biosciences site

Durham, North Carolina, United States

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Cellectar Biosciences

Canton, Ohio, United States

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Cellectar Biosciences site

Cincinnati, Ohio, United States

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Cellectar Biosciences Site

Charleston, South Carolina, United States

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Cellectar Biosciences

Greenville, South Carolina, United States

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Cellectar Biosciences site

Knoxville, Tennessee, United States

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Cellectar Biosciences site

Dallas, Texas, United States

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Cellectar Biosciences site

Dallas, Texas, United States

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Cellectar Biosciences site

Houston, Texas, United States

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Cellectar Biosciences site

Seattle, Washington, United States

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Cellectar Biosciences site

Madison, Wisconsin, United States

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Cellectar Biosciences site

Concord, New South Wales, Australia

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Cellectar Biosciences

Adelaide, South Australia, Australia

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Cellectar Biosciences

Salvador, Estado de Bahia, Brazil

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Cellectar Biosciences

Curitiba, Paraná, Brazil

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Cellectar Biosciences

Porto Alegre, RioGrande Do Sul, Brazil

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Cellectar Biosciences

Blumenau, Santa Catarina, Brazil

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Cellectar Biosciences Site

Hradec Králové, , Czechia

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Cellectar Biosciences

Helsinki, , Finland

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Cellectar Biosciences

Pessac, , France

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Cellectar Biosciences

Poitiers, , France

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Cellectar Biosciences site

Athens, , Greece

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Cellectar Biosciences Site

Rio, , Greece

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Cellectar Biosciences Site

Jerusalem, , Israel

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Cellectar Biosciences

Barcelona, , Spain

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Cellectar Biosciences site

Barcelona, , Spain

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Cellectar Biosciences

Madrid, , Spain

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Cellectar Biosciences

Madrid, , Spain

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Cellectar Biosciences

Salamanca, , Spain

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Cellectar Biosciences site

Zaragoza, , Spain

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Cellectar Biosciences

Ankara, , Turkey (Türkiye)

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Cellectar Biosciences

Bornova, , Turkey (Türkiye)

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Cellectar Biosciences

Istanbul, , Turkey (Türkiye)

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Cellectar Biosciences site

London, , United Kingdom

Site Status

Countries

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United States Australia Brazil Czechia Finland France Greece Israel Spain Turkey (Türkiye) United Kingdom

Other Identifiers

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DCL-16-001

Identifier Type: -

Identifier Source: org_study_id

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