Clinical Trial 21392

• Overview

  Study Title:

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

  Summary:

  Part A of this study evaluates iopofosine I 131 (CLR 131) in patients with select B-cell malignancies (multiple myeloma( MM), indolent chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma (LPL)/Waldenstrom Macroglobulinemia (WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), and central nervous system lymphoma (CNSL) who have been previously treated with standard therapy for their underlying malignancy. Part B (CLOVER-WaM) is a pivotal efficacy study evaluating IV administration of iopofosine I 131 in patients with WM that have received at least two prior lines of therapy.

  Objective:

  The primary objective of the study is to determine the clinical benefit rate (CBR) following the infusion of CLR 131 in patients with R/R select B-cell malignancies, including MM, CLL/SLL, LPL/WM, MZL, MCL, DLBCL and CNSL, who have had progressive or persistent neoplastic disease despite receiving standard of care for the underlying neoplasm or who are intolerant to the standard of care, based on the response criteria for the respective neoplasm under study.

• Treatments

  Therapies:

  Radiotherapy

  Medications:

  CLR 131 ()

• Inclusion Criteria

  Inclusion Criteria:
  • 18 years of age or older CLOVER 1
  • Histologically or cytologically confirmed MM; Patients with primary or secondary CNSL may be enrolled.
  • ECOG performance status of 0 to 2
  • Life expectancy of at least 6 months
  • Adequate organ and bone marrow function
  • 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 as defined in protocol
  • Measurable disease as defined in protocol CLOVER-WaM:
  • 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)
  • 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

• Exclusion Criteria

  Exclusion Criteria: CLOVER-1
  • 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
  • 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)

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