Clinical trial NCT02226965: PNT2258 for Treatment of Patients With r/r DLBCL (Wolverine)
Official title: A Phase II Study of PNT2258 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Diffuse Large B-Cell
Keywords: PNT2258
DLBCL
Diffuse Large B-cell Lymphoma
NHL
Non-Hodgkin's Lymphoma
Lymphoma
Lead sponsor: Sierra Oncology LLC - a GSK company
Sponsor class: INDUSTRY
First posted: 2014-08-27
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate
timeFrame: 19 months
Secondary outcomes:
measure: Disease Control Rate
timeFrame: 19 months
measure: Time to Response
timeFrame: 19 months
measure: Progression-free Survival
timeFrame: 19 months
measure: Safety - Assessment of Adverse Events
timeFrame: 36 months
measure: Overall Survival
timeFrame: 19 months
measure: Duration of Overall Response
timeFrame: 19 months
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Long Beach Memorial Medical Center
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Denver
country: United States
facility: Colorado Blood and Cancer Institute
state: Colorado
city: Boca Raton
country: United States
facility: Lynn Cancer Institute
state: Florida
city: Winter Haven
country: United States
facility: Bond Clinic, P.A.
state: Florida
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Lafayette
country: United States
facility: Horizon Oncology Research, Inc.
state: Indiana
city: Lafayette
country: United States
facility: UHC Oncology
state: Louisiana
city: Cumberland
country: United States
facility: Western Maryland Health System
state: Maryland
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Grand Rapids
country: United States
facility: Mercy Health Saint Mary's
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: St. John Hospital and Medical Center
state: Michigan
city: Lansing
country: United States
facility: Michigan State University
state: Michigan
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greenville
country: United States
facility: Bon Secours Saint Francis Cancer Center
state: South Carolina
city: Sioux Falls
country: United States
facility: Avera Research Institute
state: South Dakota
city: Dallas
country: United States
facility: Baylor Research Institute
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
city: Tyler
country: United States
facility: Tyler Hematology Oncology
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Newport News
country: United States
facility: Peninsula Cancer Institute
state: Virginia
city: Spokane
country: United States
facility: Medical Oncology Associates, PS
state: Washington
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion
Study officials:
affiliation: Sierra Oncology LLC - a GSK company
name: Barbara Klencke, MD
role: STUDY_CHAIR
References: