Study of CLR 131 in Relapsed or Refractory Select B-Cell Malignancies (CLOVER-1)
- Inclusion Criteria: All Patients - Histologically or cytologically confirmed MM; CLL/SLL, LPL, MZL; or MCL OR histologically proven, DLBCL. Patients with transformed DLBCL are allowed. - 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 ≥ 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 intolerable to such agents or ineligible to receive such agents. - 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. - Measurable plasmacytoma or extramedullary disease - 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. 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. 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. 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. 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 - 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) - Anti-cancer therapy within two weeks of initial CLR 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. - 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
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.
Trial Phase Phase II
Trial Type Treatment
Cellectar Biosciences, Inc.
- Primary ID DCL-16-001
- Secondary IDs NCI-2017-01758
- Clinicaltrials.gov ID NCT02952508