A Phase Ib Study of Oral Selinexor in Adult Patients With Relapsed/Refractory B-cell Lymphoma Receiving R-DHAOx or R-GDP (SELINDA)
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).
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Phase Ib Study of Oral Selinexor in Adult Patients With Relapsed/Refractory B-cell Lymphoma Receiving R-DHAOx or R-GDP|
- Incidence rate of dose-limiting toxicities (DLTs) observed during the DLT assessment period (cycle 1) at each dose level examined [ Time Frame: Up to 35 days ]
- Response rates [ Time Frame: 3 months ]Response rates will be evaluated according to the Lugano 2014 response criteria based on disease response assessment on Positron emission tomography-computed tomography (PET-CT) performed after completion of the 3 cycles of treatment (for patients who received all 3 cycles) or at permanent discontinuation of treatment (PTD evaluation, within 4 weeks after the last drug administration).
- Duration of response [ Time Frame: 3 years ]Duration of response is defined as the time of attainment of complete response (CR) or partial response (PR) to the date of first documented disease progression, relapse or death from any cause.
- Progression-free survival (PFS) [ Time Frame: 3 years ]PFS is defined as the time from inclusion into the study to the first observation of documented disease progression or death due to any cause.
- Time to next anti-lymphoma treatment (TTNLT) [ Time Frame: 3 years ]TTNLT is defined as the time from the date of inclusion to the date of first documented administration of any new anti-lymphoma treatment (chemotherapy, radiotherapy, radio-immunotherapy or immunotherapy, with the exception of High Dose Therapy/ASCT).
- Overall survival (OS) [ Time Frame: 3 years ]Overall survival is defined as the time from the date of inclusion to the date of death from any cause.
- Incidence of grade ≥ 2 renal toxicities, grade ≥ 2 neuropathy, and grade ≥ 3 toxicities [ Time Frame: 3 months ]
|Actual Study Start Date:||October 2016|
|Estimated Study Completion Date:||December 2019|
|Estimated Primary Completion Date:||January 2018 (Final data collection date for primary outcome measure)|
Experimental: 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).
Other Name: KPT-330Drug: Rituximab Drug: Dexamethasone Drug: Oxaliplatin Drug: Cisplatin Drug: Cytarabine Drug: Gemcitabine
Please refer to this study by its ClinicalTrials.gov identifier: NCT02741388
|Contact: Chloé Gourc Berthod||+334 72 66 93 33|
|Institut Jules Bordet||Recruiting|
|Contact: Marie MAEREVOET, MD +32 25 41 32 12|
|Principal Investigator: Marie MAEREVOET, MD|
|Contact: Olivier CASASNOVAS, MD +33380295041|
|Principal Investigator: Olivier CASASNOVAS, MD|
|CHRU de Lille - Hôpital Claude Huriez||Recruiting|
|Contact: Franck MORSCHHAUSER, MD +33320445713|
|Principal Investigator: Franck MORSCHHAUSER, MD|
|CHU Montpellier - Hôpital Saint Eloi||Recruiting|
|Contact: Guillaume CARTRON, MD +33467338079|
|Principal Investigator: Guillaume CARTRON, MD|
|CHU Nancy - Hôpital de Brabois||Recruiting|
|Contact: Pierre FEUGIER, MD +33383153282|
|Principal Investigator: Pierre FEUGIER, MD|
|Contact: Catherine THIEBLEMONT, MD +33142499236|
|Principal Investigator: Catherine THIEBLEMONT, MD|
|CHU Bordeaux - Centre François Magendie||Recruiting|
|Contact: Kamal BOUABDALLAH +33557656511|
|Principal Investigator: Kamal BOUABDALLAH, MD|
|Centre Henri Becquerel||Recruiting|
|Contact: Hervé TILLY, MD +33232082202|
|Principal Investigator: Hervé TILLY, MD|
|Study Chair:||Hervé TILLY, MD||Centre Henri Becquerel, Rouen, France - LYSA|
|Study Chair:||Marie MAEREVOET, MD||Institut Jules Bordet, Bruxelles, Belgium - LYSA|