PNT2258 for Treatment of Patients With r/r DLBCL (Wolverine)

• ClinicalTrials.gov Identifier: NCT02226965
• Recruitment Status: Unknown
• First Posted: August 27, 2014
• Last Update Posted: March 15, 2017
• Sponsor: Sierra Oncology, Inc.
• Information provided by (Responsible Party): Sierra Oncology, Inc.

Study Description

Brief Summary:

This study is sponsored by Sierra Oncology, Inc. formerly ProNAi Therapeutics, Inc. It is a multi-center, nonrandomized, open label, phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with relapsed or refractory (r/r) diffuse large B-cell lymphoma.

Condition or disease	Intervention/treatment	Phase
Lymphoma, Diffuse Large B-Cell	Drug: PNT2258	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 61 participants
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of PNT2258 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
• Study Start Date: December 2014
• Actual Primary Completion Date: September 2016
• Estimated Study Completion Date: July 2018

Arms and Interventions

Arm

Intervention/treatment

Experimental: PNT2258; PNT2258 will be administered at 120 mg/m2 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 8 "induction" cycles of therapy. Subjects with CR/CMR, PR/PMR or SD/NMR at the end-of-cycle 8 scan then receive ongoing PNT2258 therapy at a dose of 100 mg/m2 on days 1-4 of a 28 day cycle until progressive disease, the occurrence of unacceptable toxicity, non-compliance, voluntary withdrawal or if in the opinion of the investigator the subject is no longer benefiting from exposure to PNT2258.

Drug: PNT2258; Other Name: DNAi, BCL2 targeted therapy

Outcome Measures

Primary Outcome Measures :

1. Overall response rate [ Time Frame: 6 months ]

Secondary Outcome Measures :

1. Disease control rate [ Time Frame: 6 months ]
2. Time to response [ Time Frame: 12 months ]
3. Progression-free survival [ Time Frame: 24 months ]
4. Safety [ Time Frame: 24 months ]
   Safety will be assessed by standard CTCAE criteria
5. Overall survival [ Time Frame: 24 months ]
6. Duration of overall response [ Time Frame: 24 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Histologically confirmed diffuse large B-cell lymphoma that is refractory to prior therapy or relapsed after prior therapy.

FDG PET-CT (disease) positive baseline scan with measurable disease.

The patient must have received prior therapy that included:

• CD20-targeted therapy (for example, rituximab),
• Alkylating agent (for example, cyclophosphomide), and
• Steroid, unless the patient is steroid intolerant

Exposure to at least 1 or 2 (but no more than 3) prior systemic cytotoxic chemotherapeutic regimens.

Note: Only those subjects who are not eligible for high-dose chemotherapy and autologous stem cell transplant (HD-ASCT), or who refuse HD-ASCT, are eligible with exposure to only 1 prior cytotoxic chemotherapeutic regimen.

ECOG performance status of 0-1.

The patient must be a stable baseline with CTCAE grade ≤ 2 regarding any acute or chronic toxicity associated with prior therapy, and have discontinued prior anti-cancer therapy for ≥ 14 days prior to C1D1; mitomycin-C for at least 6 weeks prior to C1D1; SCT ≥ 2 months prior to C1D1.

Note: Palliative steroids for control of disease-related symptoms are allowed and maintenance hormone therapy is allowed.

Adequate organ function including:

• Hematologic: ANC ≥ 0.5 x 10^9/L. and platelets ≥ 50 x 10^9/L.
• Hepatic: Total Bilirubin ≤ 2 x ULN (patients with Gilbert's syndrome must have total bilirubin ≤ 3 x ULN) and serum transaminase levels ≤ 2.5 x ULN. In the case of known liver metastasis (i.e., radiological or biopsy documented), serum transaminase levels must be ≤ 5 x ULN.
• Renal: Serum creatinine ≤ 2 x ULN, or creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels above 2 x ULN.

Willingness to: 1.) undergo pre-treatment biopsy to obtain adequate tissue for analysis (e.g., core needle, excisional or incisional tumor biopsy) or 2.) provide archived tumor (e.g., FFPE block) for analysis.

Exclusion Criteria:

Eligibility for high-dose chemotherapy (HDT) and stem cell transplant (SCT). Note: Subjects who progressed ≥ 2 months after HDT/SCT are eligible

Concurrent malignancies requiring treatment.

Primary mediastinal (thymic) large B-cell lymphoma

Symptomatic CNS or leptomeningeal involvement of lymphoma.

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 patient or impair the assessment of the study results.

Signs or symptoms of heart failure characterized as greater than NYHA Class II or other significant cardiac abnormalities.

Pregnant or breast-feeding.

Prior exposure to PNT2258.

Life expectancy less than 3 months.

Contacts and Locations

  Show 27 Study Locations

Sponsors and Collaborators

Sierra Oncology, Inc.

Investigators

• Study Chair: Barbara Klencke, MD; Sierra Oncology, Inc.

More Information

• Responsible Party: Sierra Oncology, Inc.
• ClinicalTrials.gov Identifier: NCT02226965 History of Changes
• Other Study ID Numbers: PNT2258-03-DLBCL
• First Posted: August 27, 2014
• Last Update Posted: March 15, 2017
• Last Verified: March 2017

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

Keywords provided by Sierra Oncology, Inc.:

PNT2258; DLBCL; Diffuse Large B-cell Lymphoma; NHL; Non-Hodgkin's Lymphoma; Lymphoma

Additional relevant MeSH terms:

Lymphoma; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases