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

NCT02088541 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: KCP-330-008
• Study Type: interventional
• Target: 317
• Locations: 11 countries
• Sites: 78

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.

Conditions

Acute Myeloid Leukemia (AML)

Keywords

Relapsed/Refractory Acute Myeloid Leukemia; Acute Myeloid Leukemia; AML; Karyopharm; Selinexor; KPT-330

Outcome Measures

Primary Outcomes (1)

• Overall Survival

  Overall survival was defined as the time (in days) from the date of randomization to the date of death due to any cause. Participants last known to be alive were censored at date of last contact.

  Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

Secondary Outcomes (11)

• Percentage of Participants With Overall Survival of at Least 3 Months (OS3.0)

  From randomization (Day 1) up to 3 months

• Percentage of Participants With Complete Remission Rate (CRR) for Those Who Achieved Complete Remission (CR)

  Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

• Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission (CR)

  Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

• Percentage of Participants With Modified Complete Remission Rate (mCRR) for Those Who Achieved Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (Cri)

  Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

• Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission or CR With Incomplete Hematologic Recovery (CRi) or Complete Remission With Incomplete Platelet Recovery (CRp)

  Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)

Study Arms (5)

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

EXPERIMENTAL

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).

Drug: Selinexor

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

EXPERIMENTAL

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).

Drug: Selinexor

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

EXPERIMENTAL

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).

Drug: Selinexor

Physician's Choice 1 (PV <5)

ACTIVE COMPARATOR

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.

Drug: Hydroxyurea

Physician's Choice 2 (PV >=5)

ACTIVE COMPARATOR

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.

Drug: Ara-C

Interventions

Selinexor DRUG

Selinexor oral tablet.

Also known as: KPT-330

Selinexor 60 mg (PV <5) (Equivalent to 35 mg/m^2); Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2); Selinexor approximately 55 mg/m^2 (60 to 120 mg based on BSA)

Hydroxyurea DRUG

Also known as: Hydroxycarbamide

Physician's Choice 1 (PV <5)

Ara-C DRUG

Ara-C Subcutaneous Injection.

Also known as: Cytarabine, Cytosine arabinoside, Cytosar-U, Depocyt

Physician's Choice 2 (PV >=5)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Karyopharm Therapeutics Inc: lead

Study Sites (78)

Jonsson Comprehensive Cancer Center / University of California, Los Angeles

Los Angeles, California, 90024, United States

Location

Sutter Oncology & Hematology

Sacramento, California, 95816, United States

Location

Stanford Cancer Institute / Stanford University

Stanford, California, 94304, United States

Location

Colorado Blood Cancer Institute/Sarah Cannon Research Institute

Denver, Colorado, 80218, United States

Location

Yale Cancer Center / Yale University

New Haven, Connecticut, 06510, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Winship Cancer Institute / Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

University of Kansas Hospital

Kansas City, Kansas, 66160, United States

Location

Sidney Kimmel Comprehensive Cancer Center / John Hopkins University

Baltimore, Maryland, 21287, United States

Location

University of Massachusetts Medical School

Worcester, Massachusetts, 01655, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109-0944, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Westchester Medical Center / New York Medical College

Hawthorne, New York, 10532, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

New York Presbyterian Hospital / Weill Cornell Medical College

New York, New York, 10065, United States

Location

Duke Cancer Care

Durham, North Carolina, 27705, United States

Location

Gabrail Cancer Center

Canton, Ohio, 44718, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Milton S. Hershey Medical Center / Penn State

Hershey, Pennsylvania, 17033, United States

Location

Tennessee Oncology/Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Vanderbilt-Ingram Cancer Center / Vanderbilt University

Nashville, Tennessee, 37215, United States

Location

MD Anderson Cancer Center / University of Texas

Houston, Texas, 77030, United States

Location

Texas Transplant Institute/Sarah Cannon Research Institute

San Antonio, Texas, 78229, United States

Location

Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2G3, Canada

Location

Sir Mortimer B. Davis Jewish General Hospital / McGill University

Montreal, Quebec, H2W1S6, Canada

Location

Aarhus University Hospital

Aarhus, Denmark

Location

Department of Haematology, National University Hospital, Rigshospitalet

Copenhagen, Denmark

Location

Herlev Hospital

Herlev, Denmark

Location

Odense University Hospital, Department of Hematology

Odense, Denmark

Location

CHU Bordeaux- Hôpital Haut Lévêque

Bordeaux, France

Location

Centre Hospitalier Lyon

Lyon, France

Location

Hopital Saint Louis

Paris, France

Location

Hôpital Avicenne

Paris, France

Location

Institut Universitaire du Cancer Toulouse

Toulouse, France

Location

Stellvertretende Klinikleiterin Charité, Campus Benjamin Franklin

Berlin, 12203, Germany

Location

Ev. Diakonie-Krankenhaus Gemeinnutzige GMBH Medizinische Klinik 2

Bremen, Germany

Location

UNIVERSITÄTSKLINIKUM TU DRESDEN Medizinische Klinik und Poliklinik I,

Dresden, Germany

Location

University Hospital Frankfurt

Frankfurt, Germany

Location

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

Hanover, Germany

Location

Abteilung Hämatologie, internistische Onkologie und Hämostaseologie

Leipzig, Germany

Location

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

Münster, Germany

Location

Universitätsklinikum Ulm

Ulm, Germany

Location

Sororka MC

Beersheba, 85025, Israel

Location

Rambam Health Care Campus

Haifa, 3109601, Israel

Location

Wolfson Medical Center

Holon, Israel

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Rabin Medical Center

Petah Tikva, 4941492, Israel

Location

Tel Aviv Sourasky Medical Centre

Tel Aviv, Israel

Location

Chaim Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

AOU Ospedali Riuniti di Ancona

Ancona, Italy

Location

A.O Spedali Civili di Brescia

Brescia, Italy

Location

AORN Cardarelli / UOSC di Ematologia con TMO

Naples, Italy

Location

AMC, Academisch Medisch Centrum Afdeling Klinische Hematologie

Amsterdam, Netherlands

Location

VU University Medical Center

Amsterdam, Netherlands

Location

Universitair Medisch Centrum Groningen Department of Haematology

Groningen, Netherlands

Location

Radboud University Medical Center Department of Haematology (476)

Nijmegen, Netherlands

Location

Erasmus MC, location Daniel den Hoed

Rotterdam, Netherlands

Location

University Medical Center Utrecht

Utrecht, Netherlands

Location

Isala Kliniecken Zwolle

Zwolle, Netherlands

Location

Wojewódzki Szpital Specjalistyczny im. M. Kopernika, Klinika Hematologii

Lodz, Poland

Location

Samodzielny Publiczny Zakład Opieki Zdrowotnej Ministerstwa Spraw Wewnętrznych

Olsztyn, Poland

Location

Instytut Hematologii i Transfuzjologii

Warsaw, Poland

Location

Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu

Wroclaw, Poland

Location

ICO Badalona

Badalona, 08916, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital Universitario de Salamanca Servicio de Hematologia

Salamanca, Spain

Location

Hospital Universitario y Politécnico La Fe

Valencia, Spain

Location

Northwick Park Hospital

Harrow, England, HA1 3UJ, United Kingdom

Location

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

Liverpool, Lancashire, L7 8XP, United Kingdom

Location

Royal Marsden NHS Trust

Sutton, Surrey, SM2 5PT, United Kingdom

Location

University Hospital Wales

Cardiff, Wales, CF14 4XW, United Kingdom

Location

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

Hull, Yorkshire, HU3 2JZ, United Kingdom

Location

Ninewells Hospital and Medical School NHS Tayside

Dundee, DD1 9SY, United Kingdom

Location

Plymouth Hospitals NHS Trust/Derriford Hospital

Plymouth, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 34323164 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

selinexor; Hydroxyurea; Cytarabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Results Point of Contact

• Title: Jatin Shah, MD
• Organization: Karyopharm Therapeutics Inc.

jshah@karyopharm.com

(617) 658-0600

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 9, 2014
• First Posted: March 17, 2014
• Study Start: March 1, 2014
• Primary Completion: January 8, 2018
• Study Completion: January 8, 2018
• Last Updated: January 26, 2023
• Results First Posted: October 8, 2020

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

GB (7); US (26); IL (7); CA (3); DE (8); PL (4); DK (4); FR (5); IT (3); NL (7); ES (4)