PNT2258 for Treatment of Patients With Richter's Transformation (Brighton)
PNT2258 for Treatment of Patients With Richter's Transformation (Brighton)
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.
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.