Richter's Transformation
Conditions
Keywords
PNT2258, Richter's Transformation, NHL, Non-Hodgkin's Lymphoma, Lymphoma, DLBCL, Diffuse Large B-cell Lymphoma, Lymphoma, Large B-cell, Diffuse, Lymphoma, Non-Hodgkin, Lymphoma, B-cell
Brief summary
This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It is a multi-center, single-arm, 2-stage, open-label phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with Richter's Transformation.
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. Histologically confirmed Richter's transformation (RT) from chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). 2. Availability of fresh or archived tumor tissue. 3. FDG PET-CT (disease) positive baseline scan with measurable disease. 4. ECOG performance status of 0-1. 5. Evidence of disease progression at study entry. 6. Discontinuation of prior anticancer therapy for ≥ 7 days prior to C1D1 and recovered to ≤ CTCAE grade 2 (or baseline) from any acute or chronic toxicity associated with prior therapy. 7. Must have previously received at least one prior chemotherapeutic regimen for RT. \- Previously untreated RT patients deemed ineligible for, or that refuse, intensive chemotherapy are eligible. 8. Adequate bone marrow, renal, and hepatic function. 9. Normal Coagulation profile. 10. Agreement to use acceptable methods of contraception during the study and for ≥ 120 days after the last dose of PNT2258 if sexually active and able to bear or beget children. 11. Ability to participate in the clinical study for a minimum of at least 2 cycles (6 weeks).
Exclusion criteria
1. Concurrent non-hematologic malignancies requiring treatment. 2. No more than 2 prior regimens for DLBCL. 3. Hodgkin's variant of Richter's lymphoma, accelerated CLL, composite lymphoma, interdigitating dendritic cell sarcoma, sarcoma, EBV-associated lymphoma or prolymphocytic transformation. 4. Ongoing risk of bleeding. 5. CNS or leptomeningeal involvement of lymphoma 6. 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 subject or impair the assessment of the study results. 7. Pregnancy or breast-feeding. 8. Previous exposure to PNT2258.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 2 months | Proportion of subjects with complete response (CR/CMR) or partial response (PR/PMR) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Overall Response | 2 months | — |
| Time to Response | 2 months | — |
| Disease Control Rate | 2 months | Proportion of subjects with stable disease or better (CR/CMR, PR/PMR or SD/NMR) |
| Overall Survival | 2 months | — |
| Safety - Assessment of Adverse Events | 2 months | — |
| Progression Free Survival | 2 months | — |
Countries
United States
Participant flow
Recruitment details
The study was initiated in August 2015 and the first subject was enrolled on 27 October 2015. Enrollment was closed as of 07 June 2016. Subjects were enrolled at oncology clinics in the USA.
Participants by arm
| Arm | Count |
|---|---|
| PNT2258 PNT2258 administered at 120 mg/m2 on days 1-5 of a 21-day cycle for 8 induction cycles followed by continuation phase therapy at a dose of 100 mg/m2 on days 1-4 of a 28-day cycle. | 5 |
| Total | 5 |
Baseline characteristics
| Characteristic | PNT2258 |
|---|---|
| Age, Continuous | 73 years |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 4 / 5 |
Outcome results
Primary
Overall Response Rate
Proportion of subjects with complete response (CR/CMR) or partial response (PR/PMR)
Time frame: 2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PNT2258 | Overall Response Rate | 0 Participants |
Secondary
Disease Control Rate
Proportion of subjects with stable disease or better (CR/CMR, PR/PMR or SD/NMR)
Time frame: 2 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PNT2258 | Disease Control Rate | 0 Participants |
Secondary
Duration of Overall Response
Time frame: 2 months
Population: Analysis not performed as there were no responders.
Secondary
Overall Survival
Time frame: 2 months
Population: Analysis not performed as the study was terminated.
Secondary
Progression Free Survival
Time frame: 2 months
Population: Analysis not performed as the study was terminated.
Secondary
Safety - Assessment of Adverse Events
Time frame: 2 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PNT2258 | Safety - Assessment of Adverse Events | 5 participants reporting at least 1 AE |
Secondary
Time to Response
Time frame: 2 months
Population: Analysis not performed as there were no responders.