Selinexor (KPT-330) in Older Patients With Relapsed AML

NCT ID: NCT02088541

Last Updated: 2023-01-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 317 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2018-01-08

Brief Summary

This is a randomized, multicenter, open-label, phase 2 study of the SINE compound, selinexor given orally versus specified investigator choices (one of three potential salvage therapies). Participants age ≥ 60 years with relapsed or refractory AML of any type except for AML M3, after one prior therapy only, who have never undergone and who are not currently eligible for stem cell transplantation and are currently deemed unfit for intensive chemotherapy.

Detailed Description

This is a randomized, multicenter, open-label phase 2 study of the SINE compound, selinexor given orally versus restricted investigator choice (i.e., one of three potential salvage therapies).

Participants who have never been transplant eligible, are currently deemed unfit for intensive chemotherapy, ≥ 60 years old, who have AML (except Acute Promyelocytic Leukemia: APL, AML M3) after one prior treatment of either hypomethylating agent or a regimen including Ara-C, and are meeting the inclusion and exclusion criteria will be randomized to receive either oral selinexor or physician's choice (one of three potential treatments: best supportive care (BSC) alone, or BSC + hypomethylating agent, or BSC + low dose Ara-C until disease progression, death or intolerance has occurred.

Conditions

Acute Myeloid Leukemia (AML)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Selinexor approximately 55 mg/m^2 (60 to 120 mg based on BSA)

Participants under protocol versions (PV) less than (\<) 5.0 (those who had one prior line of acute myeloid leukemia (AML) therapy), receive oral selinexor tablets at a dose of approximately 55 mg/m\^2 (milligrams per square meter) (60 to 120 mg based on body surface area \[BSA\]) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle).

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

Selinexor oral tablet.

Selinexor 60 mg (PV <5) (Equivalent to 35 mg/m^2)

Participants under PV \< 5.0 (those who had one prior line of AML therapy), receive oral selinexor tablets at a fixed dose of 60 mg (equivalent to 35 mg/m\^2), based on BSA, twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle).

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

Selinexor oral tablet.

Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2)

Participants under PV \>= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), receive oral selinexor tablets at a dose of 60 mg (equivalent to 35 mg/m\^2) twice weekly, on Day 1 and 3 of each week of 4-week cycle (28 days per cycle).

Group Type: EXPERIMENTAL

Selinexor

Intervention Type: DRUG

Selinexor oral tablet.

Physician's Choice 1 (PV <5)

Participants under PV \< 5.0 (those who had one prior line of AML therapy) received Best Supportive Care (BSC) which included blood product transfusions, antimicrobials, growth factors as needed, and hydroxyurea.

Group Type: ACTIVE_COMPARATOR

Hydroxyurea

Intervention Type: DRUG

Physician's Choice 2 (PV >=5)

Participants under PV \>= 5 (PV 5: those who had at least one prior line of AML therapy, PV 5.1: who had at least two prior line of AML therapy), received BSC along with subcutaneous injection of arabinoside cytosine (Ara-C), 20 mg, twice daily, for 10 days, repeated at 28 to 42 day intervals.

Group Type: ACTIVE_COMPARATOR

Ara-C

Intervention Type: DRUG

Ara-C Subcutaneous Injection.

Interventions

Selinexor

Selinexor oral tablet.

Intervention Type: DRUG

Hydroxyurea

Intervention Type: DRUG

Ara-C

Ara-C Subcutaneous Injection.

Intervention Type: DRUG

Other Intervention Names

KPT-330; Hydroxycarbamide; Cytarabine; Cytosine arabinoside; Cytosar-U; Depocyt

Eligibility Criteria

Inclusion Criteria

• Age ≥ 60 years with relapsed or refractory AML of any type except for acute promyelocytic leukemia (APL; AML M3), after at least 1 prior AML therapy , who have never undergone, and who are not currently eligible for, stem cell transplantation, and are currently deemed unfit for intensive chemotherapy.
• Eastern Cooperative Oncology Group (ECOG) ≤ 2.
• Must have available archival or recently acquired bone marrow biopsy/aspiration or tumor tissue for central review to be eligible.
• Relapsed or refractory AML, defined as either: recurrence of disease after a complete remission (CR), or failure to achieve CR with initial therapy.
• Must have received at least 1 prior line of AML therapy given at standard doses and must have progressed after their most recent therapy. Prior therapy must have included: a hypomethylating agent with at least 2 cycles.
• At least 2 weeks must have elapsed since the last anti-leukemia treatment (with the exception of hydroxyurea) before first dose in this study.

Exclusion Criteria

• Treatment with any investigational agent within 3 weeks prior to first dose in this study.
• Presence of central nervous system (CNS) leukemia.
• In blast transformation of chronic myeloid leukemia (CML). Prior myelodysplastic syndrome (MDS) is acceptable; prior treatment for MDS does not count as an AML therapy.
• Major surgery within 2 weeks of first dose of study drug. Participants must have recovered from the effects of any surgery performed greater than 2 weeks previously.
• Concurrent active malignancy under treatment.
• Known active hepatitis B virus (HBV) or C virus (HCV) infection; or known to be positive for HCV ribonucleic acid (RNA) or HBsAg (HBV surface antigen).
• Known HIV infection.
• Unable to swallow tablets, or participants with malabsorption syndrome, or any other disease significantly affecting gastrointestinal function.
• Participants whose AML is classified as favorable according to the European LeukemiaNet (ELN) disease risk assessment.

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Karyopharm Therapeutics Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Jonsson Comprehensive Cancer Center / University of California, Los Angeles

Los Angeles, California, United States

Sutter Oncology & Hematology

Sacramento, California, United States

Stanford Cancer Institute / Stanford University

Stanford, California, United States

Colorado Blood Cancer Institute/Sarah Cannon Research Institute

Denver, Colorado, United States

Yale Cancer Center / Yale University

New Haven, Connecticut, United States

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, United States

Winship Cancer Institute / Emory University

Atlanta, Georgia, United States

Northwestern University

Chicago, Illinois, United States

University of Chicago Medicine

Chicago, Illinois, United States

University of Kansas Hospital

Kansas City, Kansas, United States

Sidney Kimmel Comprehensive Cancer Center / John Hopkins University

Baltimore, Maryland, United States

University of Massachusetts Medical School

Worcester, Massachusetts, United States

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Westchester Medical Center / New York Medical College

Hawthorne, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

New York Presbyterian Hospital / Weill Cornell Medical College

New York, New York, United States

Duke Cancer Care

Durham, North Carolina, United States

Gabrail Cancer Center

Canton, Ohio, United States

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Milton S. Hershey Medical Center / Penn State

Hershey, Pennsylvania, United States

Tennessee Oncology/Sarah Cannon Research Institute

Nashville, Tennessee, United States

Vanderbilt-Ingram Cancer Center / Vanderbilt University

Nashville, Tennessee, United States

MD Anderson Cancer Center / University of Texas

Houston, Texas, United States

Texas Transplant Institute/Sarah Cannon Research Institute

San Antonio, Texas, United States

Tom Baker Cancer Centre

Calgary, Alberta, Canada

University of Alberta

Edmonton, Alberta, Canada

Sir Mortimer B. Davis Jewish General Hospital / McGill University

Montreal, Quebec, Canada

Aarhus University Hospital

Aarhus, , Denmark

Department of Haematology, National University Hospital, Rigshospitalet

Copenhagen, , Denmark

Herlev Hospital

Herlev, , Denmark

Odense University Hospital, Department of Hematology

Odense, , Denmark

CHU Bordeaux- Hôpital Haut Lévêque

Bordeaux, , France

Centre Hospitalier Lyon

Lyon, , France

Hopital Saint Louis

Paris, , France

Hôpital Avicenne

Paris, , France

Institut Universitaire du Cancer Toulouse

Toulouse, , France

Stellvertretende Klinikleiterin Charité, Campus Benjamin Franklin

Berlin, , Germany

Ev. Diakonie-Krankenhaus Gemeinnutzige GMBH Medizinische Klinik 2

Bremen, , Germany

UNIVERSITÄTSKLINIKUM TU DRESDEN Medizinische Klinik und Poliklinik I,

Dresden, , Germany

University Hospital Frankfurt

Frankfurt, , Germany

Medizinische Hochschule Hannover (Hannover Medical School) Dept. of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation

Hanover, , Germany

Abteilung Hämatologie, internistische Onkologie und Hämostaseologie

Leipzig, , Germany

UNIVERSITY HOSPITAL OF MÜNSTER Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster

Münster, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Sororka MC

Beersheba, , Israel

Rambam Health Care Campus

Haifa, , Israel

Wolfson Medical Center

Holon, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Rabin Medical Center

Petah Tikva, , Israel

Tel Aviv Sourasky Medical Centre

Tel Aviv, , Israel

Chaim Sheba Medical Center

Tel Litwinsky, , Israel

AOU Ospedali Riuniti di Ancona

Ancona, , Italy

A.O Spedali Civili di Brescia

Brescia, , Italy

AORN Cardarelli / UOSC di Ematologia con TMO

Naples, , Italy

AMC, Academisch Medisch Centrum Afdeling Klinische Hematologie

Amsterdam, , Netherlands

VU University Medical Center

Amsterdam, , Netherlands

Universitair Medisch Centrum Groningen Department of Haematology

Groningen, , Netherlands

Radboud University Medical Center Department of Haematology (476)

Nijmegen, , Netherlands

Erasmus MC, location Daniel den Hoed

Rotterdam, , Netherlands

University Medical Center Utrecht

Utrecht, , Netherlands

Isala Kliniecken Zwolle

Zwolle, , Netherlands

Wojewódzki Szpital Specjalistyczny im. M. Kopernika, Klinika Hematologii

Lodz, , Poland

Samodzielny Publiczny Zakład Opieki Zdrowotnej Ministerstwa Spraw Wewnętrznych

Olsztyn, , Poland

Instytut Hematologii i Transfuzjologii

Warsaw, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu

Wroclaw, , Poland

ICO Badalona

Badalona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital Universitario de Salamanca Servicio de Hematologia

Salamanca, , Spain

Hospital Universitario y Politécnico La Fe

Valencia, , Spain

Northwick Park Hospital

Harrow, England, United Kingdom

Royal Liverpool University Hospital, Dept of Cellular and Molecular Physiology, Molecular and Clinical Cancer Medicine

Liverpool, Lancashire, United Kingdom

Royal Marsden NHS Trust

Sutton, Surrey, United Kingdom

University Hospital Wales

Cardiff, Wales, United Kingdom

Hull and East Yorkshire Hospitals NHS Trust Queens Centre for Oncology and Haematology

Hull, Yorkshire, United Kingdom

Ninewells Hospital and Medical School NHS Tayside

Dundee, , United Kingdom

Plymouth Hospitals NHS Trust/Derriford Hospital

Plymouth, , United Kingdom

Countries

United States; Canada; Denmark; France; Germany; Israel; Italy; Netherlands; Poland; Spain; United Kingdom

References

Sweet K, Bhatnagar B, Dohner H, Donnellan W, Frankfurt O, Heuser M, Kota V, Liu H, Raffoux E, Roboz GJ, Rollig C, Showel MM, Strickland SA Jr, Vives S, Tang S, Unger TJ, Joshi A, Shen Y, Alvarez MJ, Califano A, Crochiere M, Landesman Y, Kauffman M, Shah J, Shacham S, Savona MR, Montesinos P. A 2:1 randomized, open-label, phase II study of selinexor vs. physician's choice in older patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma. 2021 Dec;62(13):3192-3203. doi: 10.1080/10428194.2021.1950706. Epub 2021 Jul 29.

Reference Type: DERIVED

PMID: 34323164 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

KCP-330-008

Identifier Type: -

Identifier Source: org_study_id