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

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

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.

Study Overview

• Status: Terminated
• Conditions: Richter's Transformation
• Intervention / Treatment: Drug: PNT2258

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University Feinberg School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Hackensack University Medical Center
  • New York
    • New York, New York, United States, 10027
      • Columbia University Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania, Abramson Cancer Center
  • Texas
    • Tyler, Texas, United States, 75701
      • Tyler Hematology Oncology
  • Washington
    • Seattle, Washington, United States, 98122
      • Swedish Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed Richter's transformation (RT) from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
2. Availability of fresh or archived tumor tissue.
3. FDG PET-CT (disease) positive baseline scan with measurable disease.
4. ECOG performance status of 0-1.
5. Evidence of disease progression at study entry.
6. 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.

7. 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.

8. Adequate bone marrow, renal, and hepatic function.
9. Normal Coagulation profile.
10. 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.
11. Ability to participate in the clinical study for a minimum of at least 2 cycles (6 weeks).

Exclusion Criteria:

1. Concurrent non-hematologic malignancies requiring treatment.
2. No more than 2 prior regimens for DLBCL.
3. Hodgkin's variant of Richter's lymphoma, accelerated CLL, composite lymphoma, interdigitating dendritic cell sarcoma, sarcoma, EBV-associated lymphoma or prolymphocytic transformation.
4. Ongoing risk of bleeding.
5. CNS or leptomeningeal involvement of lymphoma
6. 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.
7. Pregnancy or breast-feeding.
8. Previous exposure to PNT2258.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PNT2258; 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

What is the study measuring?

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
Progression Free Survival		2 months
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
Overall Survival		2 months
Safety - Assessment of Adverse Events		2 months

Collaborators and Investigators

• Sponsor: Sierra Oncology LLC - a GSK company
• Investigators: Study Chair: Barbara Klencke, MD, Sierra Oncology LLC - a GSK company

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: February 26, 2015
• First Submitted That Met QC Criteria: February 26, 2015
• First Posted (Estimated): March 4, 2015

Study Record Updates

• Last Update Posted (Actual): June 29, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: DLBCL; Lymphoma; NHL; Lymphoma, Non-Hodgkin; Non-Hodgkin's Lymphoma; Diffuse Large B-cell Lymphoma; Richter's Transformation; Lymphoma, B-cell; PNT2258; Lymphoma, Large B-cell, Diffuse
• Other Study ID Numbers: PNT2258-04-Richter's

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO