Ensayos clínicos

Inclusion Criteria - All Patients:

• Histologically or cytologically confirmed MM; CLL/SLL, LPL/WM, MZL; or MCL OR histologically proven, DLBCL (the subtype or any molecular characterization, if available, should be recorded).
• Patients with transformed DLBCL are allowed. Patients with primary or secondary CNSL may be enrolled.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2.
• Patient is 18 years of age or older.
• Life expectancy of at least 6 months.
• Patient must meet the following laboratory criteria: o 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 m^2 (as calculated using the Cockcroft-Gault formula);
  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN);
  • Bilirubin < 1.5 × ULN;
  • Partial thromboplastin time (PTT) < 1.3 × 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 must agree to use a highly effective method of contraception during the study and for 12 months following administration of the study drug. Highly effective methods of contraception include combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, vasectomized partner, or sexual abstinence;
  • Women who have undergone hysterectomy, bilateral oophorectomy, or bilateral tubal ligation, or are post-menopausal (no menses for 12 months without an alternative medical cause) are considered to be of non-childbearing potential;
  • Men who are able to father a child must agree to use a condom during the study and for 12 months following administration of the study drug.

Exclusion Criteria:

• Ongoing Grade 2 or greater toxicities due to previous therapies. However, stable, tolerable Grade 2 AEs (e.g., neuropathy) may be allowed after discussion with the Medical Monitor.
• Prior external-beam RT resulting in greater than 20% of total bone marrow receiving greater than 20 Gy. For estimation purposes, the following bone marrow percentages can be used:
  • Vertebral bodies: Cervical 0.5%, thoracic 1%, lumbar 2% per vertebral body;
  • Hemipelvis (ilium, acetabulum, ischium): 13% per side;
  • Sacrum: 10%;
  • Skull: 12%;
  • Scapula: 5% per side;
  • Ribs: 4% per side
  • femur: 3% per side.
• 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/WM, or MZL, transformation to a more aggressive form of NHL.
• Ongoing chronic immunosuppressive therapy.
• Clinically significant bleeding event, as judged by Investigator, within prior 6 months.
• Ongoing anti-platelet therapy (except low-dose aspirin [e.g., 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. Bisphosphonates and denosumab are permitted if the patient has been receiving the medication for at least 90 days.
• 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.
• Active COVID-19 infection with positive test, including patients who are asymptomatic. Patients with prior exposure or infection who are antibody positive, but with no evidence of active COVID-19 disease would be eligible.
• For patients with primary or secondary CNSL, active bleeding in the tumor bed and/or uncontrolled seizure activity.
• Major surgery within 6 weeks of enrollment
• History of hypersensitivity to thyroid protection medication (e.g., potassium iodide, Lugol’s solution, etc.).
• Known history of human immunodeficiency virus, hepatitis C, or hepatitis B infection.
• Presence of active infection within 72 hours prior to dosing; patients with ongoing use of prophylactic antibiotics, antifungals, or antivirals are eligible as long as there is no evidence of active infection and the antibiotics, antifungals, or antivirals are not included on the list of prohibited medications.
• Pregnancy or breast-feeding.