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

NCT ID: NCT02226965

Last Updated: 2023-06-29

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-12-31

Study Completion Date

2018-08-22

Brief Summary

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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.

Detailed Description

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Conditions

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Lymphoma, Diffuse Large B-Cell

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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PNT2258

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.

Group Type EXPERIMENTAL

PNT2258

Intervention Type DRUG

Interventions

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PNT2258

Intervention Type DRUG

Other Intervention Names

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DNAi, BCL2 targeted therapy

Eligibility Criteria

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Inclusion Criteria

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.

Willingness to: 1.) undergo pre-treatment biopsy to obtain adequate tissue for analysis (e.g., core needle, excisional or incisional tumor biopsy) or 2.) provide archived tumor (e.g., FFPE block) for analysis.

Exclusion Criteria

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sierra Oncology LLC - a GSK company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Barbara Klencke, MD

Role: STUDY_CHAIR

Sierra Oncology LLC - a GSK company

Locations

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Long Beach Memorial Medical Center

Long Beach, California, United States

Site Status

University of Southern California

Los Angeles, California, United States

Site Status

Colorado Blood and Cancer Institute

Denver, Colorado, United States

Site Status

Lynn Cancer Institute

Boca Raton, Florida, United States

Site Status

Bond Clinic, P.A.

Winter Haven, Florida, United States

Site Status

Georgia Regents University

Augusta, Georgia, United States

Site Status

Rush University Medical Center

Chicago, Illinois, United States

Site Status

Horizon Oncology Research, Inc.

Lafayette, Indiana, United States

Site Status

UHC Oncology

Lafayette, Louisiana, United States

Site Status

Western Maryland Health System

Cumberland, Maryland, United States

Site Status

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Mercy Health Saint Mary's

Grand Rapids, Michigan, United States

Site Status

St. John Hospital and Medical Center

Grosse Pointe Woods, Michigan, United States

Site Status

Michigan State University

Lansing, Michigan, United States

Site Status

William Beaumont Hospital

Royal Oak, Michigan, United States

Site Status

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status

Duke University

Durham, North Carolina, United States

Site Status

Bon Secours Saint Francis Cancer Center

Greenville, South Carolina, United States

Site Status

Avera Research Institute

Sioux Falls, South Dakota, United States

Site Status

Baylor Research Institute

Dallas, Texas, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

M.D. Anderson Cancer Center

Houston, Texas, United States

Site Status

Tyler Hematology Oncology

Tyler, Texas, United States

Site Status

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status

Peninsula Cancer Institute

Newport News, Virginia, United States

Site Status

Medical Oncology Associates, PS

Spokane, Washington, United States

Site Status

Fundacion de Investigacion

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

Other Identifiers

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PNT2258-03-DLBCL

Identifier Type: -

Identifier Source: org_study_id

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