A Phase 2b Open-label Study of Selinexor (KPT-330) in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)
- Conditions
- Relapsed/Refractory DLBCLMedDRA version: 20.0Level: HLTClassification code 10012819Term: Diffuse large B-cell lymphomasSystem Organ Class: 100000004851Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2014-001977-15-PL
- Lead Sponsor
- Karyopharm Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 110
1.Written informed consent signed by the patient in accordance with federal, local, and institutional guidelines. The patient must provide informed consent prior to the first screening procedure.
2.Age =18 years.
3.Eastern Cooperative Oncology Group (ECOG) performance status of =2.
4.Patients should have estimated life expectancy of >3 months at study entry.
5.Previously treated, pathologically confirmed DLBCL, NOS (whether de novo or transformed from previously diagnosed indolent lymphoma).
6.Patients must have received at least 2 but no more than 5 prior lines of systemic therapy for the treatment of their de novo or transformed DLBCL including (i) at least 1 course of anthracycline-based chemotherapy (unless absolutely contraindicated due to cardiac dysfunction, in which case other active agents such as etoposide, bendamustine or gemcitabine must have been given) and (ii) at least 1 course of anti CD20 immunotherapy (e.g., rituximab), unless contraindicated due to severe toxicity. Patients who were considered ineligible for standard multi-agent immunochemotherapy must have received at least 2 and no more than 5 prior lines of systemic therapy, including at least 1 course of anti-CD20 antibodies, and must be approved by the Medical Monitor. Prior stem cell transplantation is allowed; induction, consolidation, stem cell collection, preparative regimen and transplantation ± maintenance are considered a single line of therapy.
7.At least 3 weeks (21 days) must have elapsed since the end of patient’s most recent systemic anti DLBCL therapy (prior to Cycle 1 Day 1). Palliative localized radiation within the therapy free interval is allowed. Non chemotherapy maintenance will not be considered anti DLBCL therapy, and therefore is allowed during the therapy-free interval.
8.Patients must have measurable disease per the revised criteria for response assessment of lymphoma. Lymph nodes should be considered abnormal if the long axis is >1.5 cm, regardless of the short axis. Extranodal lesion should be considered abnormal if the long axis is >1.0 cm.
9.Female patients of child-bearing potential must have a negative serum pregnancy test at screening. Both male and female patients must agree to use highly effective methods of contraception throughout the study and for at least 90 days following the last dose. Male patients must agree not to donate sperm during the study treatment period and at least 90 days following the last dose of study treatment.
10.Adequate hematopoietic function:
a.Hemoglobin =10.0 g/dL within 14 days of starting therapy (patient may receive red blood cell (RBC) transfusion within 14 days).
b.Absolute neutrophil count =1000 cells/mm3 (use of granulocyte growth factors prior to and during the study is acceptable).
c.Platelet count =100,000/mm3 within 14 days of starting therapy (use of platelet growth factors prior to and during the study is acceptable).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 44
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 66
Patients meeting any of the following exclusion criteria are not eligible to enroll in Part 2 of this study.
1.Diffuse large B cell lymphoma with MALT lymphoma, composite lymphoma (HL + NHL), DLBCL arising from chronic lymphocytic leukemia (CLL) (Richter’s transformation), or high-grade B-cell lymphoma.
2.Primary mediastinal (thymic) large B-cell lymphoma.
3.Patients must not be eligible for high-dose chemotherapy with autologous stem cell transplantation rescue (Investigator must provide detailed documentation for ineligibility).
4.Known active central nervous system lymphoma or meningeal involvement. Patients with a history of CNS disease treated into remission may be enrolled.
5.Patients who have not recovered to Grade =1 clinically significant AEs, or to their baseline, from their most recent systemic anti DLBCL therapy.
6.Patients with active graft-versus-host disease after allogeneic stem cell transplantation. At least 4 months must have elapsed since completion of allogeneic stem cell transplantation.
7.Major surgery within 2 weeks of first dose of study treatment.
8.Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the patient’s safety.
9.Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals on Cycle 1 Day 1; however, prophylactic use of these agents is acceptable even if parenteral.
10.Patients with active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infections. Patients with active HBV are allowed if antiviral therapy for hepatitis B has been given for >8 weeks and viral load is <100 IU/mL prior to first dose of study treatment. Patients with known history of HCV or found to be HCV antibody positive on screening are allowed if there is documentation of negative viral load per institutional standard. Patients with HIV who have negative viral load per institutional standard and no history of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections in the last year are allowed.
11.Patients unable to swallow tablets, patients with malabsorption syndrome, or any other gastrointestinal disease or gastrointestinal dysfunction that could interfere with absorption of study treatment.
12.Any of the following laboratory abnormalities:
a.A circulating lymphocyte count of >50,000/µL.
b.Hepatic dysfunction: bilirubin >2.0 times the upper limit of normal (ULN) (except patients with Gilbert’s syndrome: total bilirubin of >3 x ULN) and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) >2.5 times ULN. In patients with known liver involvement of their DLBCL, AST and ALT >5 x ULN.
c.Severe renal dysfunction: estimated creatinine clearance of <15 mL/min, measured in 24 hour urine or calculated using the formula of Cockroft and Gault ([140 - Age] x Mass (kg)/ [72 x creatinine mg/dL]; multiply by 0.85 if female).
13.Female patients who are pregnant or breastfeeding.
14.Psychiatric illness or substance use that would prevent the patient from giving informed consent or being compliant with the study procedures.
15.Received strong cytochrome P450 3A (CYP3A) inhibitors =7 days prior to Day 1 dosing or strong CYP3A inducers =14 days prior to Day 1 dosing.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method