Study of PNT2258 for Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It study is a multi-center, nonrandomized, open-label, pilot Phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with relapsed or refractory lymphoma.

Detailed Description
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PNT2258 will be administered at a dose of 120 mg/m2, as a 3-hour intravenous (IV) infusion on days 1-5 of a 21-day cycle. Treatment may continue (unless there is disease progression or the occurrence of unacceptable toxicity) for a total of 6 cycles of therapy.

Official Title
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PNT2258-02: A Pilot Phase II Study of PNT2258 for Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma

Conditions
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Lymphoma, Non-Hodgkin's

Intervention / Treatment
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* Drug: PNT2258


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent must be obtained from the patient. Participants must be ≥18 years of age. Morphologically confirmed diagnosis of non-Hodgkin's lymphoma (NHL). At least a single measureable tumor mass (long axis > 1.5 cm). An FDG-PET positive baseline scan. a. A positive scan is defined per revised Cheson criteria as focal or diffuse FDG uptake above background in a location incompatible with normal anatomy or physiology, without a specific standardized uptake value cutoff. Disease that has relapsed after administration of primary therapy that included: Rituximab and CHOP, EPOCH, bendamustine or similar chemotherapy or subsequent salvage regimen. Note: Relapse is defined as progression after a complete response to therapy or radiographic evidence of active disease after a partial response or stable disease. Have received three or fewer complete courses of systemic cytotoxic regimens. Note: Rituximab (alone or in combination with cytotoxic chemotherapy) is not considered a cytotoxic regimen. No previous exposure to PNT2258. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. Have discontinued all prior anti-cancer therapies for at least 21 days; biologic therapy for at least 4 half-lives of the drug(s); radio-immunotherapy (10 weeks); autologous stem cell transplantation (SCT) (3 months) and must be at a stable baseline regarding any acute toxicity associated with prior therapy. Adequate organ function including: Hematologic Function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L prior to treatment. Platelets ≥ 100 x 109/L. Hepatic: Total Bilirubin ≤ 1.5 x ULN and serum transaminase levels ≤ 2.5 x upper limits of normal (ULN). Renal: Serum creatinine ≤2 x ULN or creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels above 2x ULN. Exclusion Criteria: Candidates for HDT and autologous SCT. Note: Patients who progressed > 3 months after high-dose therapy (HDT)/SCT are eligible. Concurrent malignancies requiring treatment. Symptomatic central nervous system (CNS) or leptomeningeal involvement of lymphoma. Concurrent serious medical conditions (as determined by the Principal Investigator) including, but not limited to, HIV-associated lymphoma; active bacterial, fungal or viral infections. Signs and symptoms of heart failure characterized as greater than New York Heart Association (NYHA) Class I. History of myocardial infarct or prolonged corrected QT (QTc) interval (>450 milliseconds (msecs) for males or >470 msecs for females) or other significant cardiac abnormalities. Women who are pregnant or breast-feeding.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PNT2258<br>PNT2258 120 mg/m2 will be administered as a 2-hour intravenous infusion on days 1-5 of a 21-day cycle. Treatment may continue (unless there is disease progression or the occurrence of unacceptable toxicity) for a total of 6 cycles of therapy. | Drug: PNT2258<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate | Subjects who had a best response of complete response or partial response as assessed by the investigator | 39 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | The time from Cycle 1 Day 1 until the date of lymphoma progression or death from any cause, or to the last date at which progression status was adequately assessed for censored observation | 39 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PNT2258, Lymphoma, Non-Hodgkin's Lymphoma, NHL