An Open-Label, Multicenter, Phase 2 Study of CLR 131 in Patients with Relapsed or Refractory (R/R) Select B-Cell Malignancies (CLOVER-1)

Verified

Overview

This study is testing an investigational drug, CLR 131, in patients who are living with multiple myeloma and certain lymphomas. It will evaluate the safety and effectiveness of CLR 131 in patients who meet study eligibility criteria and choose to enroll in the study.

CLOVER-1 is a multicenter, open-label, Phase 2 study evaluating intravenous (IV) administration of CLR 131 in patients with B-cell malignancies who have been previously treated with standard therapy for their underlying malignancy.

Multiple myeloma patients must have received at least 2 regimens, including at least 1 approved proteasome inhibitor and at least 1 approved immunomodulatory agent. Multiple myeloma patients must have measurable evidence of disease based on a serum protein electrophoresis (SPEP), 24-hour urine protein electrophoresis (UPEP), or FLC assay (non-secretors are allowed provided the Investigator details a plan to define progressive disease (PD) prior to enrollment and to assess clinical benefit after treatment).

Up to 80 patients are planned for the study. Approximately ten initial patients evaluable for response will be enrolled into each tumor cohort. The study is being done at up to 10 medical centers in the United States and is expected to last about 24 months, but may last longer.

Study Medications

All subjects will receive CLR 131. For patients with multiple myeloma you will also take dexamethasone weekly. You will receive a single injection of the study drug, CLR 131, through an intravenous injection (IV, through a catheter in a vein in your arm) over approximately 30 minutes on day 1 and day 7 of the study.

Before the infusion of CLR 131, you will start a medication (potassium iodide drops) to help reduce the radiation exposure to the thyroid gland. This medicine must be taken by mouth within 24 hours before your dose of CLR 131 and will continue for 21 days after the dose of CLR 131. Your doctor or the study team will tell you how to take this medication.

For patients with multiple myeloma your doctor will instruct you on taking dexamethasone once per week orally (by mouth). You will need to complete a diary showing when you took the medication each week and share this with the study team.

You may be allowed to receive a second cycle of CLR 131 infusions. If your doctor thinks it is appropriate, the second cycle will be given no earlier than 75 days and no later than 180 days following the first cycle of CLR 131. Your doctor or study team will let you know if you are able to receive a second cycle.

Study Visits

After the screening visit, you will have approximately 14 visits to the study site during the study. These visits will be for treatment administration and blood draws to monitor your safety.

You will be actively participating in the study for approximately 85 days as your monitored after the injection of the CLR 131. Following this initial post-infusion safety follow-up period, patients will be followed at the discretion of treating physicians.

You can stop participating at any time. However, if you decide to stop participating in the study, we encourage you to talk to the study doctor and your regular doctor first. Please notify your study doctor if you wish to stop study participation for any reason. Your progress will continue to be followed through your medical records unless you request that access to your records be limited.

SparkCures ID 871
Trial Phase Phase 2
Enrollment 80 Patients
Treatments
Trial Sponsors
  • Cellectar Biosciences
NCT Identifier

NCT02952508

Am I Eligible?

The following criteria is a partial list of reasons why patients may or may not be eligible to participate in this clinical trial. Further evaluation with a medical professional will be required to determine full eligibility.

  • Are at least 18 years old.
  • Have Relapsed or refractory multiple myeloma.
  • Have received at least 2 prior regimens, which must include at least 1 approved proteasome inhibitor (e.g., bortezomib, carfilzomib, or ixazomib) and at least 1 approved immunomodulatory agent (e.g., thalidomide, lenalidomide, or pomalidomide), with or without maintenance therapy, unless patients are ineligible to receive such agents.
  • Patients who have undergone stem cell transplant must be at least 100 days from transplant
  • Prior total body or partial-body irradiation is not allowed. Patients who have received prior low-dose total body or partial-body irradiation may be allowed on a case-by-case basis
  • Central nervous system involvement unless previously treated with surgery or radiotherapy with the patient neurologically stable and off corticosteroids
  • Anti-cancer therapy within two weeks of initial CLR 131 infusion is excluded. However, 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.

The following criteria is provided for health care professionals.

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 ≥ 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 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.
  • 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

US Trial Locations

Accepting Patients

The following is a listing of trial locations that are open and accepting patients.

Redlands Community Hospital
Redlands Community Hospital

Redlands, CA

Mayo Clinic (Jacksonville)
Mayo Clinic (Jacksonville)

Jacksonville, FL

Loyola University Medical Center - Cardinal Bernardin Cancer Center
Loyola University Medical Center - Cardinal Bernardin Cancer Center

Maywood, IL

Northwestern Medicine Cancer Center Warrenville
Northwestern Medicine Cancer Center Warrenville

Warrenville, IL

University of Kansas Cancer Center
Ochsner Medical Center
Ochsner Medical Center

Jefferson, LA

University of Rochester Medical Center - James P. Wilmot Cancer Center
University of Rochester Medical Center - James P. Wilmot Cancer Center

Rochester, NY

Prisma Health - Greenville Memorial Hospital
Prisma Health - Greenville Memorial Hospital

Greenville, SC

Fred Hutchinson Cancer Research Center
California
Redlands Community Hospital
Redlands Community Hospital

Redlands, CA

Florida
Mayo Clinic (Jacksonville)
Mayo Clinic (Jacksonville)

Jacksonville, FL

Illinois
Loyola University Medical Center - Cardinal Bernardin Cancer Center
Loyola University Medical Center - Cardinal Bernardin Cancer Center

Maywood, IL

Northwestern Medicine Cancer Center Warrenville
Northwestern Medicine Cancer Center Warrenville

Warrenville, IL

Kansas
University of Kansas Cancer Center
Louisiana
Ochsner Medical Center
Ochsner Medical Center

Jefferson, LA

New York
University of Rochester Medical Center - James P. Wilmot Cancer Center
University of Rochester Medical Center - James P. Wilmot Cancer Center

Rochester, NY

South Carolina
Prisma Health - Greenville Memorial Hospital
Prisma Health - Greenville Memorial Hospital

Greenville, SC

Washington
Fred Hutchinson Cancer Research Center
Wisconsin
UW Carbone Cancer Center - University of Wisconsin Health

Resources

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