Lymphoma, Non-Hodgkin's
Conditions
Keywords
PNT2258, Lymphoma, Non-Hodgkin's Lymphoma, NHL
Brief summary
This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It study is a multi-center, nonrandomized, open-label, pilot Phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with relapsed or refractory lymphoma.
Detailed description
PNT2258 will be administered at a dose of 120 mg/m2, as a 3-hour intravenous (IV) infusion 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 6 cycles of therapy.
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
1. Written informed consent must be obtained from the patient. 2. Participants must be ≥18 years of age. 3. Morphologically confirmed diagnosis of non-Hodgkin's lymphoma (NHL). 4. At least a single measureable tumor mass (long axis \> 1.5 cm). 5. An FDG-PET positive baseline scan. a. A positive scan is defined per revised Cheson criteria as focal or diffuse FDG uptake above background in a location incompatible with normal anatomy or physiology, without a specific standardized uptake value cutoff. 6. Disease that has relapsed after administration of primary therapy that included: 1. Rituximab and 2. CHOP, EPOCH, bendamustine or similar chemotherapy or subsequent salvage regimen. Note: Relapse is defined as progression after a complete response to therapy or radiographic evidence of active disease after a partial response or stable disease. 7. Have received three or fewer complete courses of systemic cytotoxic regimens. Note: Rituximab (alone or in combination with cytotoxic chemotherapy) is not considered a cytotoxic regimen. 8. No previous exposure to PNT2258. 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2. 10. Have discontinued all prior anti-cancer therapies for at least 21 days; biologic therapy for at least 4 half-lives of the drug(s); radio-immunotherapy (10 weeks); autologous stem cell transplantation (SCT) (3 months) and must be at a stable baseline regarding any acute toxicity associated with prior therapy. 11. Adequate organ function including: 1. Hematologic Function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L prior to treatment. Platelets ≥ 100 x 109/L. 2. Hepatic: Total Bilirubin ≤ 1.5 x ULN and serum transaminase levels ≤ 2.5 x upper limits of normal (ULN). 3. Renal: Serum creatinine ≤2 x ULN or creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels above 2x ULN.
Exclusion criteria
1. Candidates for HDT and autologous SCT. Note: Patients who progressed \> 3 months after high-dose therapy (HDT)/SCT are eligible. 2. Concurrent malignancies requiring treatment. 3. Symptomatic central nervous system (CNS) or leptomeningeal involvement of lymphoma. 4. Concurrent serious medical conditions (as determined by the Principal Investigator) including, but not limited to, HIV-associated lymphoma; active bacterial, fungal or viral infections. 5. Signs and symptoms of heart failure characterized as greater than New York Heart Association (NYHA) Class I. 6. History of myocardial infarct or prolonged corrected QT (QTc) interval (\>450 milliseconds (msecs) for males or \>470 msecs for females) or other significant cardiac abnormalities. 7. Women who are pregnant or breast-feeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 39 months | Subjects who had a best response of complete response or partial response as assessed by the investigator |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-free Survival | 39 months | The time from Cycle 1 Day 1 until the date of lymphoma progression or death from any cause, or to the last date at which progression status was adequately assessed for censored observation |
Countries
United States
Participant flow
Recruitment details
The study was initiated in November 2012 and the first subject was enrolled on 22 January 2013. A total of 15 subjects were screened. Subjects were enrolled at oncology clinics in the USA.
Participants by arm
| Arm | Count |
|---|---|
| PNT2258 PNT2258 120 mg/m2 administered on days 1-5 of a 21-day cycle. | 13 |
| Total | 13 |
Baseline characteristics
| Characteristic | PNT2258 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 65.0 Years |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 4 / 13 |
Outcome results
Primary
Overall Response Rate
Subjects who had a best response of complete response or partial response as assessed by the investigator
Time frame: 39 months
Population: All subjects who received at least 1 dose of PNT2258
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PNT2258 | Overall Response Rate | 53.8 percentage of participants |
Secondary
Progression-free Survival
The time from Cycle 1 Day 1 until the date of lymphoma progression or death from any cause, or to the last date at which progression status was adequately assessed for censored observation
Time frame: 39 months
Population: All subjects who received at least 1 dose of PNT2258
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PNT2258 | Progression-free Survival | 9.5 months |