SADAL

Trial Overview

b Open-label, Randomized Two-arm Study of

Selinexor (KPT-330) with Low Dose Dexamethasone in Patients with Relapsed /

Refractory Diffuse Large B-Cell Lymphoma(DLBCL)

A Phase 2

Inclusion criteria

1. Written informed consent in accordance with federal, local, and institutional guidelines

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. Pathologically confirmed de novo DLBCL

6. Relapsed or refractory DLBCL as defined as below:

a. Relapsed disease defined as either recurrence of disease after a complete response (CR), or progressive disease (PD) after achieving a PR or SD (See Appendix 1 for modified International Working Group Criteria; Cheson 2007)

b.Refractory disease defined as failure to achieve at least SD with any one line of therapy or with PD ≤ 3 months of their most recent chemotherapy regimen

7. Objective, documented evidence of disease progression within approximately 4 months prior to dosing using the IWG Response Criteria for NHL (Cheson 2007) must be confirmed by central imaging assessment on study entry (scans documenting progressive disease must be confirmed by central laboratory prior to randomization)

8. Patients must have previously received at least two but no more than four previous systemic multi-agent regimens for the treatment of DLBCL including at least one course of anthracycline-based chemotherapy (unless absolutely contraindicated due to cardiac dysfunction, in which case etoposide must have been given) and at least two courses of anti-CD20 immunotherapy (e.g., rituximab), unless contraindicated due to severe toxicity. Autologous or allogeneic stem cell transplantation (ASCT) with prior induction and mobilization (± post-transplant maintenance) is all considered one line of therapy.

9. Patients must have measurable disease. 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 agree to use dual methods of contraception and have a negative serum pregnancy test at screening. Male patients must use an effective barrier 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 12.2.3.1 Permitted Concomitant Medication).

 

Exclusion criteria

1. Patients who are pregnant or lactating

2. DLBCL with coexistent histologies (e.g., follicular or mucosa-associated lymphoid tissue [MALT] lymphoma) or DLBCL transformed from other malignancies

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. Patients with severe intolerance to glucocorticoids (e.g., due to uncontrolled diabetes mellitus) that are unable to receive a minimum dose of 8 mg of dexamethasone twice weekly

6. Known central nervous system (CNS) lymphoma or meningeal involvement

7. Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 2 weeks prior to Cycle 1 Day 1 or radio-immunotherapy 4 weeks prior to Cycle 1 Day 1. Patients who have recovered to Grade ≤ 1 or to their baseline from clinically significant adverse effects are allowed.

8. Patients who 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

9. Major surgery within 2 weeks of first dose of study drug

10. Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator’s opinion, could compromise the patient’s safety

11. 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

12. 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

13. Active Hepatitis B or Hepatitis C infection

14. Known human immunodeficiency virus (HIV) infection (HIV testing is not required as part of this study)

15. 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

16. Any of the following laboratory abnormalities:

• Absolute neutrophil count (ANC) <1000 cells/mm3 or platelet count <50,000/mm3. Use of granulocyte-stimulating factors and platelet growth factors prior to and during the study is acceptable

• Hepatic dysfunction: bilirubin >1.5 times the upper limit of normal (ULN) (except patients with Gilbert’s syndrome: total bilirubin of > 3 x ULN) and alanine aminotransferase (ALT) and aspartic aminotransferase (AST) >2.5 times 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]

17. Patients with a body surface area (BSA) < 1.4 m2 as calculated per Dubois 1916 or Mosteller 1987

Research Nurse

Amy Humphries

Tel: 01132068577

E-mail: [email protected]

Other trials currently active for Diffuse Large B-Cell Lymphoma

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REMoDL-B

A randomised evaluation of molecular guided therapy for Diffuse Large B-Cell Lymphoma with Borteziomib