Clinical trial NCT02378038: PNT2258 for Treatment of Patients With Richter's Transformation (Brighton)
Official title: A Phase II Study of PNT2258 in Patients With Richter's Transformation (RT)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Richter's Transformation
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
Lead sponsor: Sierra Oncology LLC - a GSK company
Sponsor class: INDUSTRY
First posted: 2015-03-04
Enrollment: 5
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, 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall Response Rate
timeFrame: 2 months
Secondary outcomes:
measure: Disease Control Rate
timeFrame: 2 months
measure: Duration of Overall Response
timeFrame: 2 months
measure: Time to Response
timeFrame: 2 months
measure: Progression Free Survival
timeFrame: 2 months
measure: Overall Survival
timeFrame: 2 months
measure: Safety - Assessment of Adverse Events
timeFrame: 2 months
Other outcomes:
Locations:
city: Orange
country: United States
facility: UC Irvine Medical Center
state: California
city: Chicago
country: United States
facility: Northwestern University Feinberg School of Medicine
state: Illinois
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania, Abramson Cancer Center
state: Pennsylvania
city: Tyler
country: United States
facility: Tyler Hematology Oncology
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
Study officials:
affiliation: Sierra Oncology LLC - a GSK company
name: Barbara Klencke, MD
role: STUDY_CHAIR
References: