Study of CLR 131 in Relapsed or Refractory Select B-Cell Malignancies

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02952508
Recruitment Status : Recruiting
First Posted : November 2, 2016
Last Update Posted : March 19, 2018
Information provided by (Responsible Party):
Cellectar Biosciences, Inc.

Brief Summary:
This study evaluates CLR 131 in patients with select B-cell malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL) who have been previously treated with standard therapy for their underlying malignancy.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Lymphoplasmacytic Lymphoma Marginal Zone Lymphoma Mantle-Cell Lymphoma Diffuse Large B Cell Lymphoma Drug: CLR 131 Phase 2

Detailed Description:

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. Success rate, defined as complete or partial response, is as low as 2% to 4% in many of these diseases, and they remain an area of a significant unmet medical need.

CLR 131 is a radioiodinated therapeutic that exploits the selective uptake and retention of phospholipid ethers (PLEs) by malignant cells. Cellectar Biosciences' novel cancer-targeted small-molecule compound (CLR1404) is radiolabeled with the isotope iodine-131 (I-131). Radioiodinated CLR1404 has been evaluated in over 60 xenograft and spontaneous (transgenic) tumor models. In all but two cases of hepatocellular carcinoma, CLR1404 demonstrated selective cancer cell uptake and retention. In various rodent tumor models, CLR 131 has also demonstrated tumor growth delay and prolongation of survival.

Based on the critical unmet medical need for effective agents with novel mechanisms of action in B-cell malignancies, the radiosensitivity of these cancers, and initial preclinical and clinical experience with radioiodinated CLR1404, Cellectar Biosciences has chosen to assess CLR 131 in a phase 2 trial.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Phase 2 Study of CLR 131 in Patients With Relapsed or Refractory (R/R) Select B-Cell Malignancies
Actual Study Start Date : July 26, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : March 2019

Arm Intervention/treatment
Experimental: CLR 131, intravenous administration
CLR 131
Drug: CLR 131
Other Name: I-131-CLR1404

Primary Outcome Measures :
  1. Clinical benefit rate [ Time Frame: 84 days ]
    Response assessment per International Uniform Response Criteria for Multiple Myeloma or Lugano Criteria for lymphoma

Secondary Outcome Measures :
  1. Preliminary efficacy - overall response rate, time to progression, overall survival [ Time Frame: 84 days ]
    Response assessment per International Uniform Response Criteria for Multiple Myeloma or Lugano Criteria for lymphoma

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

All Patients

  • Histologically or cytologically confirmed MM; CLL/SLL, LPL, MZL; or MCL OR histologically proven, de novo, DLBCL
  • ECOG performance status of 0 to 2
  • 18 years of age or older
  • Life expectancy of at least 6 months
  • Platelets ≥ 100,000/µL (if full-dose anticoagulation therapy is used, platelets ≥ 150,000/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
  • Alanine aminotransferase < 3 × 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
  • Patient is judged by the Investigator to have the initiative and means to be compliant with the protocol and be within geographical proximity to make the required study visits
  • Patient or his or her legal representative has the ability to read, understand, and provide written informed consent for the initiation of any study-related procedures
  • Female patients of childbearing potential must have a negative pregnancy test within 24 hours of dosing
  • Women of childbearing potential and men who are able to father a child must agree to use an effective method of contraception (eg, oral contraceptives, double-barrier methods such as a condom and a diaphragm, intrauterine device, Norplant, Depo-Provera) during the study and for 12 months following administration of the study drug

Patients with Multiple Myeloma

  • At least 2 prior regimens, which must include at least 1 approved proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) and at least 1 approved immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide), with or without maintenance therapy, unless patients are ineligible to receive such agents.
  • Bone marrow biopsy within 28 days of CLR 131 infusion demonstrating at least 5% plasma cell involvement
  • 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
  • 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.
    • Measurable plasmacytoma
  • Patients who are non-secretors will be considered for accrual on a case-by-case basis by the Sponsor and will require an Investigator plan to define PD prior to enrollment and to assess clinical benefit after treatment.

Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma, 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

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 Diffuse Large B-Cell Lymphoma

  • Relapsed or refractory to combination chemotherapy for DLBCL that contains rituximab and an anthracycline. 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

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
  • Extradural tumor in contact with the spinal cord or tumor located where swelling in response to therapy may impinge upon the spinal cord
  • Central nervous system involvement unless previously treated with surgery or radiotherapy with the patient neurologically stable and off corticosteroids
  • 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)
  • PTT > 1.3 × ULN
  • INR > 2.5
  • Radiation therapy, chemotherapy, immunotherapy, or investigational therapy within 2 weeks of eligibility-defining bone marrow biopsy.
  • History of hypersensitivity to iodine
  • Any other concomitant serious illness or organ system dysfunction that in the opinion of the Investigator would either compromise patient safety or interfere with the evaluation of the safety of the test drug including, but not limited to, myelodysplastic syndromes; New York Heart Association class III-IV heart disease; unstable angina pectoris; serious cardiac arrhythmia requiring medication or a pacemaker/automatic implantable cardioverter defibrillator; myocardial infarction within the past 6 months; uncontrolled hypertension; severe peripheral vascular disease; ongoing hemodialysis or peritoneal dialysis; poorly controlled severe chronic obstructive pulmonary disease; ongoing/active infection requiring antibiotics; and uncontrolled hypothyroidism or hyperthyroidism
  • Major surgery within 6 weeks of enrollment
  • Known history of human immunodeficiency virus, hepatitis C, or hepatitis B infection
  • Pregnancy or breast-feeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02952508

Contact: Kate Oliver 608-327-8125

United States, California
Cellectar Biosciences site Recruiting
Redlands, California, United States, 92373
United States, Florida
Cellectar Biosciences site Recruiting
Jacksonville, Florida, United States, 32224
United States, Illinois
Cellectar Biosciences site Recruiting
Maywood, Illinois, United States, 60153
Cellectar Biosciences site Recruiting
Warrenville, Illinois, United States, 60555
United States, Kansas
Cellectar Biosciences site Recruiting
Westwood, Kansas, United States, 66205
United States, Louisiana
Cellectar Biosciences site Recruiting
New Orleans, Louisiana, United States, 70121
United States, New York
Cellectar Biosciences site Recruiting
Rochester, New York, United States, 14642
United States, South Carolina
Cellectar Biosciences Recruiting
Greenville, South Carolina, United States, 29605
United States, Washington
Cellectar Biosciences site Recruiting
Seattle, Washington, United States, 98109
United States, Wisconsin
Cellectar Biosciences site Recruiting
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
Cellectar Biosciences, Inc.

Responsible Party: Cellectar Biosciences, Inc. Identifier: NCT02952508     History of Changes
Other Study ID Numbers: DCL-16-001
First Posted: November 2, 2016    Key Record Dates
Last Update Posted: March 19, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Multiple Myeloma
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Large B-Cell, Diffuse
Waldenstrom Macroglobulinemia
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Neoplasms, Plasma Cell
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Leukemia, B-Cell
Lymphoma, Non-Hodgkin