PNT2258 for Treatment of Patients With r/r DLBCL (Wolverine)

NCT02226965 | Completed Phase 2 Results DMC

• 1 other identifier: PNT2258-03-DLBCL
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 27

Brief 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.

Conditions

Lymphoma, Diffuse Large B-Cell

Keywords

PNT2258; DLBCL; Diffuse Large B-cell Lymphoma; NHL; Non-Hodgkin's Lymphoma; Lymphoma

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  The proportion of patients with complete response (CR/complete metabolic response \[CMR\]) or partial response (PR/partial metabolic response \[PMR\]) according to the revised 2014 International Working Group (IWG) criteria for lymphoma (Cheson 2014)

  19 months

Secondary Outcomes (6)

• Disease Control Rate

  19 months

• Time to Response

  19 months

• Progression-free Survival

  19 months

• Safety - Assessment of Adverse Events

  36 months

• Overall Survival

  19 months

Study Arms (1)

PNT2258

EXPERIMENTAL

PNT2258 will be administered at 120 mg/m2 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 8 "induction" cycles of therapy. Subjects with CR/CMR, PR/PMR or SD/NMR at the end-of-cycle 8 scan then receive ongoing PNT2258 therapy at a dose of 100 mg/m2 on days 1-4 of a 28 day cycle until progressive disease, the occurrence of unacceptable toxicity, non-compliance, voluntary withdrawal or if in the opinion of the investigator the subject is no longer benefiting from exposure to PNT2258.

Drug: PNT2258

Interventions

PNT2258 DRUG

Also known as: DNAi, BCL2 targeted therapy

PNT2258

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sierra Oncology LLC - a GSK company: lead

Study Sites (27)

Long Beach Memorial Medical Center

Long Beach, California, 90806, United States

Location

University of Southern California

Los Angeles, California, 90033, United States

Location

Colorado Blood and Cancer Institute

Denver, Colorado, 80218, United States

Location

Lynn Cancer Institute

Boca Raton, Florida, 33486, United States

Location

Bond Clinic, P.A.

Winter Haven, Florida, 33880, United States

Location

Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Horizon Oncology Research, Inc.

Lafayette, Indiana, 47905, United States

Location

UHC Oncology

Lafayette, Louisiana, 70506, United States

Location

Western Maryland Health System

Cumberland, Maryland, 21502, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Mercy Health Saint Mary's

Grand Rapids, Michigan, 49503, United States

Location

St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, 48236, United States

Location

Michigan State University

Lansing, Michigan, 48910, United States

Location

William Beaumont Hospital

Royal Oak, Michigan, 48073, United States

Location

SUNY Upstate Medical University

Syracuse, New York, 13210, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Bon Secours Saint Francis Cancer Center

Greenville, South Carolina, 29607, United States

Location

Avera Research Institute

Sioux Falls, South Dakota, 57108, United States

Location

Baylor Research Institute

Dallas, Texas, 75246, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Tyler Hematology Oncology

Tyler, Texas, 75701, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Peninsula Cancer Institute

Newport News, Virginia, 23601, United States

Location

Medical Oncology Associates, PS

Spokane, Washington, 99208, United States

Location

Fundacion de Investigacion

San Juan, 00927, Puerto Rico

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma

Interventions

PNT100

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• Barbara Klencke, MD

  Sierra Oncology LLC - a GSK company

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 26, 2014
• First Posted: August 27, 2014
• Study Start: December 1, 2014
• Primary Completion: July 11, 2016
• Study Completion: August 22, 2018
• Last Updated: June 29, 2023
• Results First Posted: April 22, 2020

Record last verified: 2023-06

Locations

US (26); PR (1)