Lymphoma, Diffuse Large B-Cell
Conditions
Keywords
PNT2258, DLBCL, Diffuse Large B-cell Lymphoma, NHL, Non-Hodgkin's Lymphoma, Lymphoma
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.
Interventions
DRUGPNT2258
Sponsors
Sierra Oncology LLC - a GSK company
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Time to Response | 19 months | The number of months from Cycle 1 Day 1 until the date of the first documented response |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
Countries
Puerto Rico, United States
Participant flow
Recruitment details
The study was initiated in December 2014 and the first subject was enrolled on 10 December 2014. A total of 60 subjects were screened. Enrollment was closed as of 07 June 2016. Subjects were enrolled at oncology clinics in the USA.
Participants by arm
| Arm | Count |
|---|---|
| PNT2258 PNT2258 was administered at a dose of 120 mg/m2, as a 3 - 4 hour intravenous (IV) infusion on days 1 through 5 of 21-day induction phase cycles (for eight cycles), followed by continuation phase therapy at a dose of 100 mg/m2, as a 2 - 3 hour intravenous (IV) infusion on days 1 through 4 of a 28-day cycle. | 45 |
| Total | 45 |
Baseline characteristics
| Characteristic | PNT2258 |
|---|---|
| Age, Continuous | 64 years |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 11 / 45 |
| other Total, other adverse events | 45 / 45 |
| serious Total, serious adverse events | 18 / 45 |
Outcome results
Primary
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)
Time frame: 19 months
Population: All enrolled population: All patients who passed the screening in the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PNT2258 | Overall Response Rate | 11.1 percentage of participants |
Secondary
Disease Control Rate
The proportion of patients who have a response of stable disease (SD/no metabolic response \[NMR\]) or better by investigator assessment
Time frame: 19 months
Population: All enrolled population: All patients who passed the screening in the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PNT2258 | Disease Control Rate | 20.0 percentage of participants |
Secondary
Duration of Overall Response
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
Time frame: 19 months
Population: All enrolled population: All patients who passed the screening in the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PNT2258 | Duration of Overall Response | 5.3 months |
Secondary
Overall Survival
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
Time frame: 19 months
Population: All enrolled population: All patients who passed the screening in the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PNT2258 | Overall Survival | 9.8 months |
Secondary
Progression-free Survival
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 frame: 19 months
Population: All enrolled population: All patients who passed the screening in the study
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PNT2258 | Progression-free Survival | 1.9 months |
Secondary
Safety - Assessment of Adverse Events
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
Time frame: 36 months
Population: Safety population: All patients who received at least 1 dose of PNT2258
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PNT2258 | Safety - Assessment of Adverse Events | 45 participants reporting at least 1 AE |
Secondary
Time to Response
The number of months from Cycle 1 Day 1 until the date of the first documented response
Time frame: 19 months
Population: All enrolled population: All patients who passed the screening in the study
| Arm | Measure | Value (MEAN) |
|---|---|---|
| PNT2258 | Time to Response | 2.2 months |