Study of Iopofosine I 131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) and Pivotal Expansion in Waldenstrom Macroglobulinemia (CLOVER-WaM)
Waldenstrom Macroglobulinemia, Multiple Myeloma, Chronic Lymphocytic Leukemia
About this trial
This is an interventional treatment trial for Waldenstrom Macroglobulinemia focused on measuring Waldenstrom Macroglobulinemia, Non-Hodgkin Lymphoma, NHL, Relapsed, Refractory, Novel class, Pivotal, Phase 3, Hematologic disease, Neoplasm, Plasma cell neoplasms, Paraproteinemias, Lymphoma, Immunoproliferative disorder, Blood protein disorders, Lymphoproliferative disorders, Antineoplastic agents
Eligibility Criteria
[CLOVER-1] Inclusion Criteria: All Patients
- Histologically or cytologically confirmed MM; Patients with primary or secondary CNSL may be enrolled.
- 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 ≥ 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 m2
- Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) ≤ 2.5 × 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
Patients with Multiple Myeloma
- At least 5 prior regimens, which must include at least 1 approved proteasome inhibitor (bortezomib, carfilzomib, or ixazomib), at least 1 approved immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide), and at least 1 approved monoclonal antibody (e.g., daratumumab or elotuzumab) with or without maintenance therapy, unless patients are intolerable to such agents or ineligible to receive such agents.
- At least triple-class refractory (refractory to a proteasome inhibitor, immunomodulatory agent, and a monoclonal antibody)
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.
[CLOSED] Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma, Lymphoplasmacytic Lymphoma/Waldenstom Macroglobulinemia, 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.
[CLOSED] 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.
[CLOSED] 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.
Patients with CNS Lymphoma
- Must have biopsy-proven disease and must have received at least one prior intervention for their disease.
- Must be at least two weeks from CNS biopsy before administration of iopofosine I 131.
- Must have at least one lesion with enhancement on brain imaging.
- Stable (or decreasing) dose of corticosteroids or anti-convulsant medication for at least 7 days prior to dosing
[CLOVER-1] 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
- 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 iopofosine I 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.
- For patients with primary or secondary CNSL, active bleeding in the tumor bed and/or uncontrolled seizure activity
[CLOVER-WaM] Inclusion Criteria
- Histologically or cytologically confirmed WM. Patients with a diagnosis of LPL may be enrolled with prior Sponsor approval.
- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2 (Appendix C)
- Patient is 18 years of age or older
- Life expectancy of at least 6 months
- Received at least two prior lines of therapy for WM
- Measurable IgM (above upper limit of normal) OR at least one measurable nodal lesion with longest diameter > 15 mm or one measurable extranodal lesion (e.g., hepatic nodule) with longest diameter > 10 mm
[CLOVER-WaM] Exclusion Criteria
- Ongoing Grade 2 or greater toxicities due to previous therapies, excluding alopecia.
- 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.)
- Patients with second malignancies in addition to WM, if the second malignancy has required therapy in the last 2 years or is not in remission; exceptions to this criterion include successfully treated non-metastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy
- Anti-cancer therapy within two weeks of initial iopofosine I 131 infusion.
- Need for acute treatment of WM (e.g., those with hyperviscosity)
Sites / Locations
- Cellectar Biosciences siteRecruiting
- Cellectar Biosciences siteRecruiting
- Cellectar Biosciences siteRecruiting
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- Cellectar Biosciences siteRecruiting
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- Cellectar Biosciences site
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- Cellectar Biosciences siteRecruiting
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- Cellectar Biosciences site
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- Cellectar BiosciencesRecruiting
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- Cellectar Biosciences SiteRecruiting
- Cellectar BiosciencesRecruiting
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- Cellectar Biosciences siteRecruiting
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- Cellectar Biosciences siteRecruiting
- Cellectar Biosciences site
- Cellectar Biosciences siteRecruiting
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- Cellectar BiosciencesRecruiting
- Cellectar BiosciencesRecruiting
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- Cellectar BiosciencesRecruiting
- Cellectar Biosciences SiteRecruiting
- Cellectar BiosciencesRecruiting
- Cellectar BiosciencesRecruiting
- Cellectar BiosciencesRecruiting
- Cellectar Biosciences siteRecruiting
- Cellectar Biosciences SiteRecruiting
- Cellectar Biosciences SiteRecruiting
- Cellectar BiosciencesRecruiting
- Cellectar Biosciences siteRecruiting
- Cellectar BiosciencesRecruiting
- Cellectar BiosciencesRecruiting
- Cellectar BiosciencesRecruiting
- Cellectar Biosciences siteRecruiting
- Cellectar BiosciencesRecruiting
- Cellectar BiosciencesRecruiting
- Cellectar BiosciencesRecruiting
- Cellectar Biosciences siteRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Experimental
Experimental
Experimental
Experimental
Iopofosine I 131, intravenous administration WM
Iopofosine I 131, intravenous administration MM
Iopofosine I 131, intravenous administration CNS Lymphoma
Iopofosine I 131 intravenous administration NHL [CLOSED]
Iopofosine I 131 in Waldenstroms Macroglobulinemia
Iopofosine I 131 in Multiple Myeloma
Iopofosine I 131 in Central Nervous System Lymphoma
Iopofosine I 131 in Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma, Mantle Cell Lymphoma, Marginal Zone Lymphoma, and Diffuse Large B-Cell Lymphoma