Phase I Trial of Selinexor (KPT-330) and Ifosfamide, Carboplatin, Etoposide (ICE) in Peripheral T-cell Lymphoma

NCT03212937 | Completed Phase 1

• 1 other identifier: Karyopharm001
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, open-label, phase I trial with a standard 3+3 dose escalation schema to identify the maximum tolerated dose (MTD) of selinexor when combined with ICE. Once MTD is determined, there will be an expansion phase and tumor biopsies and peripheral blood will be taken pre and post selinexor to examine the study's biologic objectives.

Conditions

Peripheral T-cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment related dose limiting toxicity as assessed by NCI CTCAE v4.0

  The first 3 weeks of treatment

Secondary Outcomes (3)

• Overall response rate

  From the start of treatment to the best overall response of Complete or Partial Response is achieved, up to 2 years

• Progression-free survival

  From the start of the treatment to the date of documentation of either disease progression or death, up to 2 years

• Overall survival

  From the start of treatment to the date of death from any cause, up to 2 years

Study Arms (1)

Selinexor and ICE Chemotherapy

EXPERIMENTAL

Drug: Selinexor; Drug: ICE Chemotherapy

Interventions

Selinexor DRUG

Oral KPT-330 is administered on Day 3, 5, and 7 of each 21-day cycle. Starting dose is 40mg will be adjusted according to toxicity

Selinexor and ICE Chemotherapy

ICE Chemotherapy DRUG

IV Ifosfamide 5g/m\^2 on Day 2 (inpatient) or D1 (outpatient) of each 21-day cycle IV Carboplatin AUC 5 on Day 2 (inpatient) or D1-3 (outpatient) of each 21-day cycle IV Etoposide 100 mg/m\^2 on Days 1-3 of each 21-day cycle

Also known as: Ifosfamide, Carboplatin, Etoposide

Selinexor and ICE Chemotherapy

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically confirmed T or NK/T-cell lymphomas including the following histologies:
• Peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS)
• Angioimmunoblastic T-cell lymphomas (AITL)
• Anaplastic large cell lymphoma (ALCL)
• Natural-killer/T-cell lymphoma (NKTL)
• Patients must have received at least two cycles of one prior regimen administered with curative intent and one of the following:
• failed to have achieve at least a partial response after 2 or more cycles
• failed to achieve a complete response after 6 or more cycles
• progressed after an initial response
• For patients who have CD30+ anaplastic large cell lymphoma, they must have failed or are ineligible or intolerant of brentuximab vedotin
• Patients must be age \>18 years.
• Patients must have at least one site of measurable disease, 1.5 cm in diameter or greater.
• Patients must have ECOG performance status of 0-2
• Patients must have laboratory test results within these ranges:
• Absolute neutrophil count ≥1500/mm³

You may not qualify if:

• Patients who have had prior malignancies (other than T and NK/T-cell lymphomas) for ≤5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast.
• Patients who have had other anti-cancer therapy, including radiation or experimental drug or therapy, within 28 days of enrollment.
• Patients with known HIV, active hepatitis B, active hepatitis C.
• Patients with known central nervous system involvement by lymphoma.
• Patients with known or suspected hypersensitivity to selinexor.
• Men and women of all ethnic groups are eligible for this study

Sponsors & Collaborators

• National Cancer Centre, Singapore: lead

Study Sites (1)

National Cancer Centre Singapore

Singapore, 169610, Singapore

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

selinexor; ICE protocol 5; Ifosfamide; Carboplatin; Etoposide

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cyclophosphamide; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Tiffany PL Tang

  National Cancer Centre, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2017
• First Posted: July 11, 2017
• Study Start: July 1, 2016
• Primary Completion: November 1, 2020
• Study Completion: November 1, 2020
• Last Updated: April 28, 2021

Record last verified: 2021-04

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)