Selinexor (KPT-330) in Older Patients With Relapsed AML (SOPRA)
Acute Myeloid Leukemia (AML)
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring Relapsed/Refractory Acute Myeloid Leukemia, Acute Myeloid Leukemia, AML, Karyopharm, Selinexor, KPT-330
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.
Sites / Locations
- Jonsson Comprehensive Cancer Center / University of California, Los Angeles
- Sutter Oncology & Hematology
- Stanford Cancer Institute / Stanford University
- Colorado Blood Cancer Institute/Sarah Cannon Research Institute
- Yale Cancer Center / Yale University
- H. Lee Moffitt Cancer Center and Research Institute
- Winship Cancer Institute / Emory University
- Northwestern University
- University of Chicago Medicine
- University of Kansas Hospital
- Sidney Kimmel Comprehensive Cancer Center / John Hopkins University
- University of Massachusetts Medical School
- University of Michigan Comprehensive Cancer Center
- Hackensack University Medical Center
- Roswell Park Cancer Institute
- Westchester Medical Center / New York Medical College
- Memorial Sloan Kettering Cancer Center
- New York Presbyterian Hospital / Weill Cornell Medical College
- Duke Cancer Care
- Gabrail Cancer Center
- Ohio State University Comprehensive Cancer Center
- Milton S. Hershey Medical Center / Penn State
- Tennessee Oncology/Sarah Cannon Research Institute
- Vanderbilt-Ingram Cancer Center / Vanderbilt University
- MD Anderson Cancer Center / University of Texas
- Texas Transplant Institute/Sarah Cannon Research Institute
- Tom Baker Cancer Centre
- University of Alberta
- Sir Mortimer B. Davis Jewish General Hospital / McGill University
- Aarhus University Hospital
- Department of Haematology, National University Hospital, Rigshospitalet
- Herlev Hospital
- Odense University Hospital, Department of Hematology
- CHU Bordeaux- Hôpital Haut Lévêque
- Centre Hospitalier Lyon
- Hopital Saint Louis
- Hôpital Avicenne
- Institut Universitaire du Cancer Toulouse
- Stellvertretende Klinikleiterin Charité, Campus Benjamin Franklin
- Ev. Diakonie-Krankenhaus Gemeinnutzige GMBH Medizinische Klinik 2
- UNIVERSITÄTSKLINIKUM TU DRESDEN Medizinische Klinik und Poliklinik I,
- University Hospital Frankfurt
- Medizinische Hochschule Hannover (Hannover Medical School) Dept. of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation
- Abteilung Hämatologie, internistische Onkologie und Hämostaseologie
- UNIVERSITY HOSPITAL OF MÜNSTER Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster
- Universitätsklinikum Ulm
- Sororka MC
- Rambam Health Care Campus
- Wolfson Medical Center
- Hadassah Medical Center
- Rabin Medical Center
- Tel Aviv Sourasky Medical Centre
- Chaim Sheba Medical Center
- AOU Ospedali Riuniti di Ancona
- A.O Spedali Civili di Brescia
- AORN Cardarelli / UOSC di Ematologia con TMO
- AMC, Academisch Medisch Centrum Afdeling Klinische Hematologie
- VU University Medical Center
- Universitair Medisch Centrum Groningen Department of Haematology
- Radboud University Medical Center Department of Haematology (476)
- Erasmus MC, location Daniel den Hoed
- University Medical Center Utrecht
- Isala Kliniecken Zwolle
- Wojewódzki Szpital Specjalistyczny im. M. Kopernika, Klinika Hematologii
- Samodzielny Publiczny Zakład Opieki Zdrowotnej Ministerstwa Spraw Wewnętrznych
- Instytut Hematologii i Transfuzjologii
- Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu
- ICO Badalona
- Hospital del Mar
- Hospital Universitario de Salamanca Servicio de Hematologia
- Hospital Universitario y Politécnico La Fe
- Northwick Park Hospital
- Royal Liverpool University Hospital, Dept of Cellular and Molecular Physiology, Molecular and Clinical Cancer Medicine
- Royal Marsden NHS Trust
- University Hospital Wales
- Hull and East Yorkshire Hospitals NHS Trust Queens Centre for Oncology and Haematology
- Ninewells Hospital and Medical School NHS Tayside
- Plymouth Hospitals NHS Trust/Derriford Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Active Comparator
Active Comparator
Selinexor approximately 55 mg/m^2 (60 to 120 mg based on BSA)
Selinexor 60 mg (PV <5) (Equivalent to 35 mg/m^2)
Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2)
Physician's Choice 1 (PV <5)
Physician's Choice 2 (PV >=5)
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).
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).
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).
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.
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.