Clinical trial NCT01733238: Study of PNT2258 for Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma
Official title: PNT2258-02: A Pilot Phase II Study of PNT2258 for Treatment of Relapsed or Refractory Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, Non-Hodgkin's
Keywords: PNT2258
Lymphoma
Non-Hodgkin's Lymphoma
NHL
Lead sponsor: Sierra Oncology LLC - a GSK company
Sponsor class: INDUSTRY
First posted: 2012-11-26
Enrollment: 13
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 study is a multi-center, nonrandomized, open-label, pilot Phase II investigation of PNT2258 to characterize anti-tumor activity and collect safety data on patients with relapsed or refractory lymphoma.

Detailed description: PNT2258 will be administered at a dose of 120 mg/m2, as a 3-hour intravenous (IV) infusion 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 6 cycles of therapy.

Eligibility criteria: Inclusion Criteria:

1. Written informed consent must be obtained from the patient.
2. Participants must be ≥18 years of age.
3. Morphologically confirmed diagnosis of non-Hodgkin's lymphoma (NHL).
4. At least a single measureable tumor mass (long axis \> 1.5 cm).
5. An FDG-PET positive baseline scan.

   a. A positive scan is defined per revised Cheson criteria as "focal or diffuse FDG uptake above background in a location incompatible with normal anatomy or physiology, without a specific standardized uptake value cutoff".
6. Disease that has relapsed after administration of primary therapy that included:

   1. Rituximab and
   2. CHOP, EPOCH, bendamustine or similar chemotherapy or subsequent salvage regimen.

   Note: Relapse is defined as progression after a complete response to therapy or radiographic evidence of active disease after a partial response or stable disease.
7. Have received three or fewer complete courses of systemic cytotoxic regimens. Note: Rituximab (alone or in combination with cytotoxic chemotherapy) is not considered a cytotoxic regimen.
8. No previous exposure to PNT2258.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
10. Have discontinued all prior anti-cancer therapies for at least 21 days; biologic therapy for at least 4 half-lives of the drug(s); radio-immunotherapy (10 weeks); autologous stem cell transplantation (SCT) (3 months) and must be at a stable baseline regarding any acute toxicity associated with prior therapy.
11. Adequate organ function including:

    1. Hematologic Function: absolute neutrophil count (ANC) ≥ 1.5 x 109/L prior to treatment. Platelets ≥ 100 x 109/L.
    2. Hepatic: Total Bilirubin ≤ 1.5 x ULN and serum transaminase levels ≤ 2.5 x upper limits of normal (ULN).
    3. Renal: Serum creatinine ≤2 x ULN or creatinine clearance ≥ 60 mL/min/1.73 m2 for subjects with serum creatinine levels above 2x ULN.

Exclusion Criteria:

1. Candidates for HDT and autologous SCT. Note: Patients who progressed \> 3 months after high-dose therapy (HDT)/SCT are eligible.
2. Concurrent malignancies requiring treatment.
3. Symptomatic central nervous system (CNS) or leptomeningeal involvement of lymphoma.
4. Concurrent serious medical conditions (as determined by the Principal Investigator) including, but not limited to, HIV-associated lymphoma; active bacterial, fungal or viral infections.
5. Signs and symptoms of heart failure characterized as greater than New York Heart Association (NYHA) Class I.
6. History of myocardial infarct or prolonged corrected QT (QTc) interval (\>450 milliseconds (msecs) for males or \>470 msecs for females) or other significant cardiac abnormalities.
7. Women who are pregnant or breast-feeding.

Primary outcomes:
measure: Overall Response Rate
timeFrame: 39 months
Secondary outcomes:
measure: Progression-free Survival
timeFrame: 39 months
Other outcomes:
Locations:
city: Lafayette
country: United States
facility: Horizon Oncology Research, Inc.
state: Indiana
city: Grand Rapids
country: United States
facility: Cancer and Hematology Centers of Western Michigan, P.C.
state: Michigan
city: Grosse Pointe Woods
country: United States
facility: St. John Hospital and Medical Center, Van Elslander Cancer Center
state: Michigan
Study officials:
affiliation: Sierra Oncology LLC - a GSK company
name: Barbara Klencke, M.D.
role: STUDY_CHAIR
affiliation: St. John Hospital and Medical Center, Van Elslander Cancer Center
name: Ayad Al-Katib, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Harb W, Lakhani NJ, Messmann R, Klencke B, Al-Katib AM. A Phase 2 Study of PNT2258 for Treatment of Relapsed or Refractory B-Cell Malignancies. Clin Lymphoma Myeloma Leuk. 2021 Dec;21(12):823-830. doi: 10.1016/j.clml.2021.07.016. Epub 2021 Jul 23.