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

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

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma, Non-Hodgkin's
• Intervention / Treatment: Drug: PNT2258

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Lafayette, Indiana, United States, 47905
      • Horizon Oncology Research, Inc.
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Cancer and Hematology Centers of Western Michigan, P.C.
    • Grosse Pointe Woods, Michigan, United States, 48236
      • St. John Hospital and Medical Center, Van Elslander Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Written informed consent must be obtained from the patient.
2. Participants must be ≥18 years of age.
3. Morphologically confirmed diagnosis of non-Hodgkin's lymphoma (NHL).
4. At least a single measureable tumor mass (long axis > 1.5 cm).

5. 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".

6. Disease that has relapsed after administration of primary therapy that included:

   1. Rituximab and
   2. 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.

7. 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.
8. No previous exposure to PNT2258.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
10. 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.

11. Adequate organ function including:

    1. Hematologic Function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L prior to treatment. Platelets ≥ 100 x 109/L.
    2. Hepatic: Total Bilirubin ≤ 1.5 x ULN and serum transaminase levels ≤ 2.5 x upper limits of normal (ULN).
    3. 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:

1. Candidates for HDT and autologous SCT. Note: Patients who progressed > 3 months after high-dose therapy (HDT)/SCT are eligible.
2. Concurrent malignancies requiring treatment.
3. Symptomatic central nervous system (CNS) or leptomeningeal involvement of lymphoma.
4. Concurrent serious medical conditions (as determined by the Principal Investigator) including, but not limited to, HIV-associated lymphoma; active bacterial, fungal or viral infections.
5. Signs and symptoms of heart failure characterized as greater than New York Heart Association (NYHA) Class I.
6. 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.
7. Women who are pregnant or breast-feeding.

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 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sierra Oncology LLC - a GSK company
• Investigators: Principal Investigator: Ayad Al-Katib, MD, St. John Hospital and Medical Center, Van Elslander Cancer Center; Study Chair: Barbara Klencke, M.D., Sierra Oncology LLC - a GSK company

Publications and helpful links

General Publications

• Harb W, Lakhani NJ, Messmann R, Klencke B, Al-Katib AM. A Phase 2 Study of PNT2258 for Treatment of Relapsed or Refractory B-Cell Malignancies. Clin Lymphoma Myeloma Leuk. 2021 Dec;21(12):823-830. doi: 10.1016/j.clml.2021.07.016. Epub 2021 Jul 23.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): August 1, 2016

Study Registration Dates

• First Submitted: November 20, 2012
• First Submitted That Met QC Criteria: November 24, 2012
• First Posted (Estimated): November 26, 2012

Study Record Updates

• Last Update Posted (Actual): June 22, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Lymphoma; NHL; Non-Hodgkin's Lymphoma; PNT2258
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: PNT2258-02