Clinical trial NCT02088541: Selinexor (KPT-330) in Older Patients With Relapsed AML
Official title: A Randomized, Open Label, Phase 2 Study of the Selective Inhibitor of Nuclear Export (SINE) Selinexor (KPT-330) Versus Specified Physician's Choice in Patients ≥ 60 Years Old With Relapsed or Refractory Acute Myeloid Leukemia (AML) Who Are Ineligible for Intensive Chemotherapy and/or Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Myeloid Leukemia (AML)
Keywords: Relapsed/Refractory Acute Myeloid Leukemia
Acute Myeloid Leukemia
AML
Karyopharm
Selinexor
KPT-330
Lead sponsor: Karyopharm Therapeutics Inc
Sponsor class: INDUSTRY
First posted: 2014-03-17
Enrollment: 317
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Survival
timeFrame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Secondary outcomes:
measure: Percentage of Participants With Overall Survival of at Least 3 Months (OS3.0)
timeFrame: From randomization (Day 1) up to 3 months
measure: Percentage of Participants With Complete Remission Rate (CRR) for Those Who Achieved Complete Remission (CR)
timeFrame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
measure: Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission (CR)
timeFrame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
measure: Percentage of Participants With Modified Complete Remission Rate (mCRR) for Those Who Achieved Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (Cri)
timeFrame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
measure: 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)
timeFrame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
measure: Percentage of Participants With Overall Response Rate (ORR)
timeFrame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
measure: Duration of Response (DOR)
timeFrame: Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
measure: Percentage of Participants With Disease Control Rate (DCR)
timeFrame: Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria
measure: Duration of Disease Control Rate
timeFrame: Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria
measure: Change From Baseline in Quality of Life (QoL) and Patient-Reported Outcomes (Functional Assessment of Cancer Therapy -Leukemia [FACT-Leu]
timeFrame: Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)
measure: Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Health Questionnaire Visual Analogue Scale (VAS)
timeFrame: Baseline, Day 1 of each treatment cycle (a maximum of 20 cycles: 28 days per cycle) up to 30 days after last dose of study drug (final visit)
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center / University of California, Los Angeles
state: California
city: Sacramento
country: United States
facility: Sutter Oncology & Hematology
state: California
city: Stanford
country: United States
facility: Stanford Cancer Institute / Stanford University
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute/Sarah Cannon Research Institute
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center / Yale University
state: Connecticut
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute / Emory University
state: Georgia
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center / John Hopkins University
state: Maryland
city: Worcester
country: United States
facility: University of Massachusetts Medical School
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Hawthorne
country: United States
facility: Westchester Medical Center / New York Medical College
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital / Weill Cornell Medical College
state: New York
city: Durham
country: United States
facility: Duke Cancer Care
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Comprehensive Cancer Center
state: Ohio
city: Hershey
country: United States
facility: Milton S. Hershey Medical Center / Penn State
state: Pennsylvania
city: Nashville
country: United States
facility: Tennessee Oncology/Sarah Cannon Research Institute
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center / Vanderbilt University
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center / University of Texas
state: Texas
city: San Antonio
country: United States
facility: Texas Transplant Institute/Sarah Cannon Research Institute
state: Texas
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Montreal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Hospital / McGill University
state: Quebec
city: Aarhus
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Department of Haematology, National University Hospital, Rigshospitalet
city: Herlev
country: Denmark
facility: Herlev Hospital
city: Odense
country: Denmark
facility: Odense University Hospital, Department of Hematology
city: Bordeaux
country: France
facility: CHU Bordeaux- Hôpital Haut Lévêque
city: Lyon
country: France
facility: Centre Hospitalier Lyon
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Hôpital Avicenne
city: Toulouse
country: France
facility: Institut Universitaire du Cancer Toulouse
city: Berlin
country: Germany
facility: Stellvertretende Klinikleiterin Charité, Campus Benjamin Franklin
city: Bremen
country: Germany
facility: Ev. Diakonie-Krankenhaus Gemeinnutzige GMBH Medizinische Klinik 2
city: Dresden
country: Germany
facility: UNIVERSITÄTSKLINIKUM TU DRESDEN Medizinische Klinik und Poliklinik I,
city: Frankfurt
country: Germany
facility: University Hospital Frankfurt
city: Hanover
country: Germany
facility: Medizinische Hochschule Hannover (Hannover Medical School) Dept. of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation
city: Leipzig
country: Germany
facility: Abteilung Hämatologie, internistische Onkologie und Hämostaseologie
city: Münster
country: Germany
facility: UNIVERSITY HOSPITAL OF MÜNSTER Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster
city: ULM
country: Germany
facility: Universitätsklinikum Ulm
city: Beer Sheva
country: Israel
facility: Sororka MC
city: Haifa
country: Israel
facility: Rambam Health Care Campus
city: Holon
country: Israel
facility: Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Rabin Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky Medical Centre
city: Tel Hashomer
country: Israel
facility: Chaim Sheba Medical Center
city: Ancona
country: Italy
facility: AOU Ospedali Riuniti di Ancona
city: Brescia
country: Italy
facility: A.O Spedali Civili di Brescia
city: Naples
country: Italy
facility: AORN Cardarelli / UOSC di Ematologia con TMO
city: Amsterdam
country: Netherlands
facility: AMC, Academisch Medisch Centrum Afdeling Klinische Hematologie
city: Amsterdam
country: Netherlands
facility: VU University Medical Center
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen Department of Haematology
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Center Department of Haematology (476)
city: Rotterdam
country: Netherlands
facility: Erasmus MC, location Daniel den Hoed
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Zwolle
country: Netherlands
facility: Isala Kliniecken Zwolle
city: Lodz
country: Poland
facility: Wojewódzki Szpital Specjalistyczny im. M. Kopernika, Klinika Hematologii
city: Olsztyn
country: Poland
facility: Samodzielny Publiczny Zakład Opieki Zdrowotnej Ministerstwa Spraw Wewnętrznych
city: Warszawa
country: Poland
facility: Instytut Hematologii i Transfuzjologii
city: Wroclaw
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu
city: Badalona
country: Spain
facility: ICO Badalona
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca Servicio de Hematologia
city: Valencia
country: Spain
facility: Hospital Universitario y Politécnico La Fe
city: Harrow
country: United Kingdom
facility: Northwick Park Hospital
state: England
city: Liverpool
country: United Kingdom
facility: Royal Liverpool University Hospital, Dept of Cellular and Molecular Physiology, Molecular and Clinical Cancer Medicine
state: Lancashire
city: Sutton
country: United Kingdom
facility: Royal Marsden NHS Trust
state: Surrey
city: Cardiff
country: United Kingdom
facility: University Hospital Wales
state: Wales
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire Hospitals NHS Trust Queens Centre for Oncology and Haematology
state: Yorkshire
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School NHS Tayside
city: Plymouth
country: United Kingdom
facility: Plymouth Hospitals NHS Trust/Derriford Hospital
Study officials:
References:
citation: 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.