NCT02471911

KPT-330 Plus RICE for Relapsed/Refractory Aggressive B-Cell Lymphoma

A Phase I Investigator-Initiated Study of Selinexor (KPT-330) Plus RICE in Patients With Relapsed or Refractory Aggressive B-cell Lymphomas

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 22 (actual)
• Sponsor: Weill Medical College of Cornell University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This study evaluates the addition of selinexor (KPT-330) to RICE chemotherapy in the treatment of relapsed and refractory aggressive B-Cell Lymphoma, with the goal of improved response rates (as compared to RICE chemotherapy alone).

Detailed description

Although aggressive B-cell lymphomas are potentially curable with front-line chemotherapy, at least one-third of patients experience progression or relapse. Second-line regimens such as rituximab, ifosfamide, carboplatin, and etoposide (RICE) are administered with the goal of cytoreduction prior to autologous stem cell transplantation (ASCT) in eligible patients. However, half of patients who receive salvage treatment and ASCT are still not cured. Selinexor is a Selective Inhibitor of Nuclear Export / SINE compound, which is a new class of molecule. SINE compounds have been shown to induce apoptotic cell death in pre-clinical models of AML, CLL, T-ALL, and Ph+ ALL as well as B and T-cell non-Hodgkin lymphomas. Preliminarily, selinexor has demonstrated promising single-agent clinical activity in patients with previously treated NHL including DLBCL, warranting further investigation. Based on promising preclinical and clinical data, selinexor is currently under evaluation in combination with chemotherapy for solid tumors. The investigators hypothesize that the combination of selinexor plus RICE will be well-tolerated and clinically active in participants with previously treated aggressive B-cell lymphomas and propose a phase I trial to evaluate this combination. Moreover, Investigators will evaluate primary patient samples before and after selinexor to investigate the mechanisms of action of selinexor, including the mechanisms by which selinexor sensitizes cells to chemotherapy, and evaluate other novel drug combinations in aggressive B-cell lymphomas.

Conditions

• Diffuse Large B-Cell Lymphoma

Interventions

Type	Name	Description
DRUG	KPT-330	KPT-330 administered orally on days -5 and -3 prior to starting chemotherapy. Once chemotherapy starts, KPT-330 will be administered on days 1, 3, and 5 of each cycle. Dose levels will range from 20 mg to 100mg with a standard 3+3 escalation schema.
DRUG	Rituximab	IV Rituximab 375 mg/m2 on D1
DRUG	Etoposide	IV Etoposide 100 mg/m2 on D1-3
DRUG	Carboplatin	IV Carboplatin AUC 5 on D2
DRUG	Ifosfamide	IV Ifosfamide 5 g/m2 on D2
DRUG	Dexamethasone	20 mg qd on Days -5 and -3. 20 mg qd on Days 1-5

Timeline

• Start date: 2015-12-11
• Primary completion: 2019-10-31
• Completion: 2021-10-14
• First posted: 2015-06-15
• Last updated: 2022-04-12

Locations

1 site across 1 country: United States