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 enrollment

• 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 and no more than 5, which must include at least 1 approved proteasome inhibitor (bortezomib or carfilzomib) 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%.

  • 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 and no more than 4 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 and no more than 2 prior regimens

• 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.

• One additional therapy or stem cell transplant for DLBCL is allowed.

• 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