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-BG
- Lead Sponsor
- Karyopharm Therapeutics, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 275
The study population under evaluation will consist of male and female
patients aged 18 years or older. To be included in this study, a patient
must meet all the following criteria:
1. Written informed consent 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 (Appendix 2)
4. Patients should have estimated life expectancy of >3 months at
study entry
5. Previously treated, pathologically confirmed de novo DLBCL, or
DLBCL transformed from previously diagnosed indolent lymphoma
(e.g., follicular lymphoma)
6. Patients must have received at least 2 but no more than 5 previous
systemic regimens for the treatment of their de novo or transformed
DLBCL including (i) at least one 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
one 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 two and no more than five prior treatment regimens
including at least one 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. For patients whose most recent systemic anti-DLBCL therapy
induced a PR or CR, at least 60 days must have elapsed since the end of
that therapy. For all other patients, at least 14 weeks (98 days) must
have elapsed since the end of their most recent systemic anti DLBCL
therapy. 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. Documented clinical or radiographic evidence of progressive DLBCL
prior to dosing.
9. Patients must have measurable disease per the revised criteria for
response assessment of lymphoma (Cheson
2014). Lymph nodes should be considered abnormal if the long axis is
>1.5 cm, regardless of the short axis. If a lymph node has a long axis
of
1.1 to 1.5 cm, it should only be considered abnormal if its short axis is
>1.0. Lymph nodes = 1.0 by = 1.0 will not be considered abnormal for
relapse or progressive disease.
10. Female patients of child-bearing potential must have a negative
serum pregnancy test at screening and agree to use reliable methods of
contraception for three months after their last dose of medication. Male
patients must use a reliable method of contraception if sexually active
with a female of child-bearing potential. For both male and female
patients, effective methods of contraception must be used throughout
the study and for three months following the last dose (see Section
13.5.2.1 Permitted Concomitant Medication – Prevention of Pregnancy
for description of acceptable contraceptive methods).
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 87
F.1.3 Elderly (>=65 years) yes
F.1.
Patients meeting any of the following exclusion criteria are not eligible
to enroll in this study.
1. Patients who are pregnant or lactating
2. DLBCL with mucosa-associated lymphoid tissue [MALT] lymphoma,
composite lymphoma (HL+NHL), or DLBCL transformed from diseases other than indolent NHL.
3. Primary mediastinal (thymic) large B-cell lymphoma (PMBL)
4. Patients must not be eligible for high-dose chemotherapy with autologous stem cell transplantation rescue (investigator must provide detailed documentation for ineligibility)
5. Known central nervous system (CNS) lymphoma or meningeal involvement
6. For patients whose most recent systematic anti-DLBCL therapy
induced a PR or CR: Radiation, chemotherapy, immunotherapy, radioimmunotherapy or any other anticancer therapy other than glucocorticoids < 60 days prior to Cycle 1 Day 1.
7. For patients whose most recent systemic anti-DLBCL therapy did not
induce a PR or CR: Radiation, chemotherapy, immunotherapy, radioimmunotherapy, or any other anticancer therapy other than glucocorticoids < 14 weeks prior to Cycle 1 Day 1
8. Patients who have not recovered to Grade = 1 clinically significant AEs, or to their baseline, from their most recent systemic anti DLBCL therapy
9. 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
10. Major surgery within 2 weeks of first dose of study treatment
11. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety
12. Unstable cardiovascular function:
• Symptomatic ischemia, or
• Uncontrolled clinically significant conduction abnormalities (i.e.,
ventricular tachycardia on anti-arrhythmia are excluded; 1st degree AV
block or asymptomatic LAFB/RBBB will not be excluded), or
• Congestive heart failure (CHF) of NYHA Class =3, or
• Myocardial infarction (MI) within 3 months
13. Uncontrolled (i.e., clinically unstable) infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose; however, prophylactic use of these agents is acceptable even if parenteral
14. Active Hepatitis B or Hepatitis C infection
15. Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study)
16. Patients unable to swallow tablets, patients with malabsorption syndrome, or any other GI disease or GI dysfunction that could interfere with absorption of study treatment
17. Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) <1000 cells/mm3 or platelet count
<75,000/mm3 during screening and on C1D1. Use of granulocytestimulating
factors and platelet growth factors prior to and during the study is acceptable.
• A circulating lymphocyte count of >50,000/ul
• 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.
• Severe renal dysfunction: estimated creatinine clearance of < 30
mL/min, measured in 24 hour urine or calculated using the formula of
Cockroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL);
multiply by 0.85 if female]
• Hematopoietic dysfunction:
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