PNT2258 for Treatment of Patients With r/r DLBCL (Wolverine)
Condition: Lymphoma, Diffuse Large B-Cell
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: PNT2258
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 45.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: PNT2258; DLBCL; Diffuse Large B-cell Lymphoma; NHL; Non-Hodgkin's Lymphoma; Lymphoma

Summary:

      This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It is a
      multi-center, nonrandomized, open label, phase II investigation of PNT2258 to characterize
      anti-tumor activity and collect safety data on patients with relapsed or refractory (r/r)
      diffuse large B-cell lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

        Histologically confirmed diffuse large B-cell lymphoma that is refractory to prior therapy
        or relapsed after prior therapy.

        FDG PET-CT (disease) positive baseline scan with measurable disease.

        The patient must have received prior therapy that included:

          -  CD20-targeted therapy (for example, rituximab),

          -  Alkylating agent (for example, cyclophosphomide), and

          -  Steroid, unless the patient is steroid intolerant

        Exposure to at least 1 or 2 (but no more than 3) prior systemic cytotoxic chemotherapeutic
        regimens.

        Note: Only those subjects who are not eligible for high-dose chemotherapy and autologous
        stem cell transplant (HD-ASCT), or who refuse HD-ASCT, are eligible with exposure to only 1
        prior cytotoxic chemotherapeutic regimen.

        ECOG performance status of 0-1.

        The patient must be a stable baseline with CTCAE grade ≤ 2 regarding any acute or chronic
        toxicity associated with prior therapy, and have discontinued prior anti-cancer therapy for
        ≥ 14 days prior to C1D1; mitomycin-C for at least 6 weeks prior to C1D1; SCT ≥ 2 months
        prior to C1D1.

        Note: Palliative steroids for control of disease-related symptoms are allowed and
        maintenance hormone therapy is allowed.

        Adequate organ function including:

          -  Hematologic: ANC ≥ 0.5 x 10^9/L. and platelets ≥ 50 x 10^9/L.

          -  Hepatic: Total Bilirubin ≤ 2 x ULN (patients with Gilbert's syndrome must have total
             bilirubin ≤ 3 x ULN) and serum transaminase levels ≤ 2.5 x ULN. In the case of known
             liver metastasis (i.e., radiological or biopsy documented), serum transaminase levels
             must be ≤ 5 x ULN.

          -  Renal: Serum creatinine ≤ 2 x ULN, or creatinine clearance ≥ 60 mL/min/1.73 m2 for
             subjects with serum creatinine levels above 2 x ULN.

        Willingness to: 1.) undergo pre-treatment biopsy to obtain adequate tissue for analysis
        (e.g., core needle, excisional or incisional tumor biopsy) or 2.) provide archived tumor
        (e.g., FFPE block) for analysis.

        Exclusion Criteria:

        Eligibility for high-dose chemotherapy (HDT) and stem cell transplant (SCT). Note: Subjects
        who progressed ≥ 2 months after HDT/SCT are eligible

        Concurrent malignancies requiring treatment.

        Primary mediastinal (thymic) large B-cell lymphoma

        Symptomatic CNS or leptomeningeal involvement of lymphoma.

        Concurrent clinically significant illness, medical condition, surgical history, physical
        finding, electrocardiogram or laboratory finding that, in the opinion of the investigator,
        could adversely affect the safety of the patient or impair the assessment of the study
        results.

        Signs or symptoms of heart failure characterized as greater than NYHA Class II or other
        significant cardiac abnormalities.

        Pregnant or breast-feeding.

        Prior exposure to PNT2258.

        Life expectancy less than 3 months.