PNT2258 for Treatment of Patients With Richter's Transformation (Brighton)

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 is a multi-center, single-arm, 2-stage, open-label phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with Richter's Transformation.

Official Title
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A Phase II Study of PNT2258 in Patients With Richter's Transformation (RT)

Conditions
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Richter's Transformation

Intervention / Treatment
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* Drug: PNT2258


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed Richter's transformation (RT) from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Availability of fresh or archived tumor tissue. FDG PET-CT (disease) positive baseline scan with measurable disease. ECOG performance status of 0-1. Evidence of disease progression at study entry. Discontinuation of prior anticancer therapy for ≥ 7 days prior to C1D1 and recovered to ≤ CTCAE grade 2 (or baseline) from any acute or chronic toxicity associated with prior therapy. Must have previously received at least one prior chemotherapeutic regimen for RT. - Previously untreated RT patients deemed ineligible for, or that refuse, intensive chemotherapy are eligible. Adequate bone marrow, renal, and hepatic function. Normal Coagulation profile. Agreement to use acceptable methods of contraception during the study and for ≥ 120 days after the last dose of PNT2258 if sexually active and able to bear or beget children. Ability to participate in the clinical study for a minimum of at least 2 cycles (6 weeks). Exclusion Criteria: Concurrent non-hematologic malignancies requiring treatment. No more than 2 prior regimens for DLBCL. Hodgkin's variant of Richter's lymphoma, accelerated CLL, composite lymphoma, interdigitating dendritic cell sarcoma, sarcoma, EBV-associated lymphoma or prolymphocytic transformation. Ongoing risk of bleeding. 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 subject or impair the assessment of the study results. Pregnancy or breast-feeding. Previous exposure to PNT2258.

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 will be administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle. | 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 | Proportion of subjects with complete response (CR/CMR) or partial response (PR/PMR) | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate | Proportion of subjects with stable disease or better (CR/CMR, PR/PMR or SD/NMR) | 2 months | 
| Duration of Overall Response |  | 2 months | 
| Time to Response |  | 2 months | 
| Progression Free Survival |  | 2 months | 
| Overall Survival |  | 2 months | 
| Safety - Assessment of Adverse Events |  | 2 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PNT2258, Richter's Transformation, NHL, Non-Hodgkin's Lymphoma, Lymphoma, DLBCL, Diffuse Large B-cell Lymphoma, Lymphoma, Large B-cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, B-cell