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

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).

Conditions

• B-cell Lymphoma

Interventions

DRUG

selinexor

DRUG

Rituximab

DRUG

Dexamethasone

DRUG

Oxaliplatin

DRUG

Cisplatin

DRUG

Cytarabine

DRUG

Gemcitabine

Sponsors & Collaborators

• Karyopharm Therapeutics Inc

  collaborator INDUSTRY

• The Lymphoma Academic Research Organisation

  lead OTHER

Principal Investigators

• Hervé TILLY, MD · Centre Henri Becquerel, Rouen, France - LYSA

• Marie MAEREVOET, MD · Institut Jules Bordet, Bruxelles, Belgium - LYSA

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Max Age

70 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-10-31

Primary Completion

2021-09-29

Completion

2021-09-29

Countries

• Belgium
• France

Study Locations