PNT2258 for Treatment of Patients With r/r DLBCL (Wolverine)
- Registration Number
- NCT02226965
- Lead Sponsor
- Sierra Oncology LLC - a GSK company
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description PNT2258 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.
- Primary Outcome Measures
Name Time Method Overall Response Rate 19 months 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)
- Secondary Outcome Measures
Name Time Method Disease Control Rate 19 months The proportion of patients who have a response of stable disease (SD/no metabolic response \[NMR\]) or better by investigator assessment
Progression-free Survival 19 months The number of months from C1D1 until the date of DLBCL progression or death from any cause, or to the last date at which progression status was adequately assessed for censored observation
Time to Response 19 months The number of months from Cycle 1 Day 1 until the date of the first documented response
Safety - Assessment of Adverse Events 36 months Characterization of the type, frequency, severity, timing of onset, duration, and relationship to study drug of any treatment-emergent adverse events, laboratory abnormalities, serious adverse events or adverse events leading to discontinuation of study treatment
Duration of Overall Response 19 months The time from the initial CMR or PMR until the date of progression or death from any cause, or to the last date at which progression status was adequately assessed for censored observations
Overall Survival 19 months The number of months from C1D1 until the date of death from any cause, or to the last date at which survival status was adequately assessed for censored observations
Trial Locations
- Locations (27)
Rush University Medical Center
🇺🇸Chicago, Illinois, United States
Michigan State University
🇺🇸Lansing, Michigan, United States
William Beaumont Hospital
🇺🇸Royal Oak, Michigan, United States
SUNY Upstate Medical University
🇺🇸Syracuse, New York, United States
Baylor Research Institute
🇺🇸Dallas, Texas, United States
Virginia Cancer Specialists
🇺🇸Fairfax, Virginia, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Bond Clinic, P.A.
🇺🇸Winter Haven, Florida, United States
St. John Hospital and Medical Center
🇺🇸Grosse Pointe Woods, Michigan, United States
Avera Research Institute
🇺🇸Sioux Falls, South Dakota, United States
Mercy Health Saint Mary's
🇺🇸Grand Rapids, Michigan, United States
Lynn Cancer Institute
🇺🇸Boca Raton, Florida, United States
Fundacion de Investigacion
🇵🇷San Juan, Puerto Rico
Western Maryland Health System
🇺🇸Cumberland, Maryland, United States
Georgia Regents University
🇺🇸Augusta, Georgia, United States
Horizon Oncology Research, Inc.
🇺🇸Lafayette, Indiana, United States
Peninsula Cancer Institute
🇺🇸Newport News, Virginia, United States
Tyler Hematology Oncology
🇺🇸Tyler, Texas, United States
M.D. Anderson Cancer Center
🇺🇸Houston, Texas, United States
Medical Oncology Associates, PS
🇺🇸Spokane, Washington, United States
Colorado Blood and Cancer Institute
🇺🇸Denver, Colorado, United States
Duke University
🇺🇸Durham, North Carolina, United States
Long Beach Memorial Medical Center
🇺🇸Long Beach, California, United States
University of Southern California
🇺🇸Los Angeles, California, United States
UHC Oncology
🇺🇸Lafayette, Louisiana, United States
Bon Secours Saint Francis Cancer Center
🇺🇸Greenville, South Carolina, United States
University of Texas Southwestern Medical Center
🇺🇸Dallas, Texas, United States