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A Phase Ib Study of Oral Selinexor in Adult Patients With Relapsed/Refractory B-cell Lymphoma Receiving R-DHAOx or R-GDP

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Disease Information

Descriptive Information
Brief Title † A Phase Ib Study of Oral Selinexor in Adult Patients With Relapsed/Refractory B-cell Lymphoma Receiving R-DHAOx or R-GDP
Official Title † A Phase Ib Study of Oral Selinexor in Adult Patients With Relapsed/Refractory B-cell Lymphoma Receiving R-DHAOx or R-GDP
Brief Summary This is an open label, multicenter, dose escalation, phase Ib study to determine the recommended phase II dose (RP2D), by assessing the maximum tolerated dose (MTD), safety and preliminary efficacy of selinexor in adult patients with relapsed/refractory B-cell malignancies receiving either R-DHAOx (Group A) or R-GDP (Group B). This dose escalation phase will be followed by an exploratory expansion phase in the same population with 12 patients enrolled in each group, who will receive selinexor at the RP2D. The "3+3" design will be applied for dose escalation. The escalation will be performed independently in two distinct groups: - Group A : Oral selinexor + R-DHAOx for 3 cycles (3-week cycles) - Group B: Oral selinexor + R-GDP for 3 cycles (3-week cycles) The choice of the conventional immunotherapy regimen which will be administered to each patient, R-DHAOx (Group A) or R-GDP (Group B), is left at the investigator's decision before patient's inclusion. Different dose levels for selinexor administration will be examined sequentially in each group by the Dose Escalation Committee (DEC): 4 doses of selinexor per 3-week cycle at 20 mg flat (Dose Level -1, DL-1), 40 mg flat (DL1), 60 mg flat (DL2) or 80 mg flat (DL3) will be taken orally by the patient on D1, D3, D8 and D10 of each cycle (dosing weeks = week 1 and week 2 of each 3-week cycle). Dose escalation will begin at DL1 and will continue until the MTD is exceeded or until the highest dose level defined in the study (DL3) is reached. Dose escalation to the next planned dose level will be decided by the DEC based on the number of DLTs observed during the DLT assessment period. The dose escalation phase will be followed by an exploratory expansion phase in the same two groups (Groups A and B), depending on the decision of the Independent Data Monitoring Committee (IDMC) after review of safety data at the end of dose escalation part. Patients enrolled in the expansion phase will receive selinexor at the RP2D defined by the IDMC, together with either of the conventional regimen R-DHAOx or R-GDP (left at the investigator's choice).
Detailed Description
Study Phase Phase 1
Study Type † Interventional
Study Design †
Primary Outcome Measure † Incidence rate of dose-limiting toxicities (DLTs) observed during the DLT assessment period (cycle 1) at each dose level examined
Secondary Outcome Measure † Response rates
Condition † B-cell Lymphoma
Intervention † Drugselinexor
Study Arms / Comparison Groups Selinexor + immunochemotherapy Selinexor will be administered orally on Day1, 3, 8 and 10 of each 3-week cycle with an immunochemotherapy, R-DHAOx (Group A: rituximab + dexamethasone + oxaliplatin + cytarabine) or R-GDP (Group B: rituximab + dexamethasone + gemcitabine + cisplatin) for 3 cycles (choice of the immunochemotherapy left at the investigator's decision before patient's inclusion). Different dose levels of selinexor will be examined sequentially in each group: 20 mg flat (DL-1), 40 mg flat (DL1), 60 mg flat (DL2), 80 mg flat (DL3).
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Drug
Estimated Enrollment † 60
Start Date † October 2016
Completion Date December 2019
Primary Completion Date January 2018
Eligibility Criteria † Inclusion Criteria: 1. Patients with any type of relapsed or refractory B-cell lymphoma 2. Eligible to receive R-DHAOx or R-GDP regarding the investigator's opinion 3. Who received prior therapy with at least one but no more than two lines therapies for B-Cell Lymphoma 4. Patient must have measurable disease defined by at least one single node or tumor lesion > 1.5 cm 5. Aged between 18 years and 70 years (included) on date of consent signature 6. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 7. With a life expectancy of ≥ 3 months 8. Having signed a written informed consent 9. Male patients (if sexually active with a woman of childbearing potential) must agree to use a reliable method of birth control during the study treatment and for at least 6 months after the last study drug administration. Male patients must agree to not donate sperm during the study treatment and for at least 6 months after the last study drug administration 10. Female patients of childbearing potential must agree to use two reliable methods of birth control during study treatment and for 6 months after the last dose and have a negative serum human chorionic gonadotropin (hCG) pregnancy test within 3 days prior to C1D1. Reliable methods of contraception include intrauterine devices, hormonal contraceptives [contraceptive pills, implants, transdermal patches, hormonal vaginal devices or injections with prolonged release], abstinence or sterilization of the partner. Exclusion Criteria: 1. Previous treatment with selinexor 2. Known central nervous system or meningeal involvement by lymphoma 3. Contraindication to any drug contained in these regimen 4. Subjects with known Human Immunodeficiency Virus (HIV) positivity 5. Subjects with known active Hepatitis B (HB) infection (positive Ag HBs) or positive serology to hepatitis B (Ag HBs or antibody anti-HB c or positive DNA PCR) or active Hepatitis C (HCV) infection (patients with positive HCV serology are eligible only if PCR is negative for known HCV RNA) 6. Subjects with any uncontrolled active systemic infection requiring intravenous (IV) antibiotics 7. Any of the following laboratory abnormalities within 14 days prior to first administration (C1D1) of study treatment: 1. Absolute neutrophil count (ANC) 5.0 x upper limit of normal (ULN) 4. Serum total bilirubin > 2x Upper Limit of Normal (ULN), or > 5x ULN if due to Gilbert syndrome or lymphoma involvement 8. Creatinine clearance
Gender All
Ages 18 Years - 70 Years
Accepts Healthy Volunteers No
Contacts †† Chloé Gourc Berthod, +334 72 66 93 33
Location Countries † Belgium
Administrative Information
NCT ID † NCT02741388
Organization ID SELINDA
Secondary IDs ††
Responsible Party Sponsor
Study Sponsor † The Lymphoma Academic Research Organisation
Collaborators †† Karyopharm Therapeutics, Inc
Investigators † Study Chair: Hervé TILLY, MD, Centre Henri Becquerel, Rouen, France - LYSA
Information Provided By
Verification Date March 2017
First Received Date † April 14, 2016
Last Updated Date March 8, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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