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

Sierra Oncology

Status and phase: Terminated; Phase 2

Conditions: Richter's Transformation

Treatments: Drug: PNT2258

Study type: Interventional

Funder types: Industry

Identifiers

NCT02378038

PNT2258-04-Richter's

Details and patient eligibility

About

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.

Enrollment: 5 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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5 participants in 1 patient group

PNT2258

Experimental group

Description:

PNT2258 will be 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.

Treatment:

Drug: PNT2258