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

Primary Purpose

Acute Myeloid Leukemia (AML)

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Selinexor
Hydroxyurea
Ara-C
Sponsored by
Karyopharm Therapeutics Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

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

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Arm Type

Experimental

Experimental

Experimental

Active Comparator

Active Comparator

Arm Label

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)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Percentage of Participants With Overall Survival of at Least 3 Months (OS3.0)
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. Analysis was performed using Kaplan-Meier method.
Percentage of Participants With Complete Remission Rate (CRR) for Those Who Achieved Complete Remission (CR)
CRR was analyzed using International Working Group (IWG) 2003 criteria, as the difference in the proportions of participants with IWG results of CR. CR per IWG 2003 criteria was defined as morphologic presence of < 5 percentage (%) myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood absolute neutrophil count (ANC) > 1000 cells/microliter (microL) and platelet count > 100,000/microL, with no need for red blood cell (RBC) transfusions), and the absence of extramedullary disease.
Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission (CR)
DFS for CRR based on IWG criteria, was calculated from the first date of response of CR to the date of progression or recurrence, or date of death if progression or recurrence did not occur. Participants who discontinued prior to disease progression or recurrence or did not progress as of the time of the analysis were censored at the time of last radiologic assessment. CR per IWG 2003 criteria was defined as morphologic presence of < 5 % myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease.
Percentage of Participants With Modified Complete Remission Rate (mCRR) for Those Who Achieved Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (Cri)
mCRR was defined as the point estimate of the percentage of participants who had CR, CRi, or CRp. Responses defined as per IWG 2003 response criteria: Morphologic CR:< 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.
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)
DFS based on IWG criteria was defined as the duration from start of the complete response achieved until disease progression or death from any cause. Responses defined by IWG 2003 Response Criteria: Morphologic CR: < 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.
Percentage of Participants With Overall Response Rate (ORR)
Overall response rate was defined as the point estimate of the percentage of participants who achieved CR (disappearance of all target and non-target lesions), partial response (PR) (>=30 % decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions). CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. CRp; All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L) and morphologic leukemia-free state (MLFS); morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%, in absence of blasts with Auer rods, no hematologic recovery required.
Duration of Response (DOR)
DOR was calculated from date of response of CR, CRi, CRp, MLFS, or PR to date of progression or recurrence based on IWG criteria. CR: <5% myeloblasts in bone marrow,absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL, platelet count > 100,000/microL, no need for RBC transfusions), absence of extramedullary disease. PR: No circulating blasts, neutrophil count > =1.0 x10^9/L, platelet count >= 100 x10^9/L, >= 50 % reduction in bone marrow blast to 6% to 25%, or blasts less than or equal to (<=) 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), CRi; < 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS: morphologic bone marrow blast clearance to < 5% in marrow sample, <= 200 cells enumerated/cellularity is ≥ 10%, in absence of blasts with Auer rods, no hematologic recovery required.
Percentage of Participants With Disease Control Rate (DCR)
DCR:Point estimate of % of participants with CR,CRi,CRp,MLFS,PR, or SD for <=4 weeks.CR:<5% myeloblasts in bone marrow (BM),absence of circulating blasts,hematologic recovery(peripheral blood ANC >1000 cells/microL and platelet count >100,000/microL, no need of RBC transfusions),absence of extramedullary disease. PR:No circulating blasts,Neutrophil count >=1.0 x10^9/L, Platelet count >= 100*10^9/L, >=50% reduction in BM blast to 6% to 25%, or blasts <=5% if Auer rods are present.CRp:All criteria for CR except for residual neutropenia (<1*10^9/L) or thrombocytopenia(<100 x10^9/L),CRi;< 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS:morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%,in absence of blasts with Auer rods,no hematologic recovery required,SD:failure to achieve a response but not meeting criteria for disease progression over period of >4 weeks.
Duration of Disease Control Rate
Duration of DCR calculated for all participants with DCR. CR: < 5% myeloblasts in BM, absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL and platelet count > 100,000/microL, no need for RBC transfusions), absence of extra medullary disease. PR: No circulating blasts, Neutrophil count >=1.0 x 10^9/L, Platelet count >= 100 x 10^9/L, >= 50 % reduction in BM blast to 6% to 25%, or blasts <= 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1 x 10^9/L) or thrombocytopenia (<100 x 10^9/L), CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS; morphologic BM blast clearance to < 5% in a marrow sample in which <=200 cells enumerated/cellularity is >= 10%, in absence of blasts with Auer rods, no hematologic recovery required and SD; failure to achieve a response but not meeting criteria for disease progression over period of > 4 weeks.
Change From Baseline in Quality of Life (QoL) and Patient-Reported Outcomes (Functional Assessment of Cancer Therapy -Leukemia [FACT-Leu]
QoL was assessed by the FACT-Leu. FACT-Leu combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific sub-scale (17 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI; total of 31 items) was the primary measurement of interest, comprising the Physical and Functional sub-scales plus the leukemia - specific sub-scale. Each item was rated on a 5-point Likert scale. Range from 0 = (Not at all) to 4 = (Very much); therefore, the TOI had a score ranging from 0 to 124. Higher scores indicated improvement in well being. The QoL assessment was performed at baseline (prior to first dose of study treatment), Day 1 of each cycle on or after the second, and at the final visit.
Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Health Questionnaire Visual Analogue Scale (VAS)
EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.

Full Information

First Posted
March 9, 2014
Last Updated
January 24, 2023
Sponsor
Karyopharm Therapeutics Inc
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1. Study Identification

Unique Protocol Identification Number
NCT02088541
Brief Title
Selinexor (KPT-330) in Older Patients With Relapsed AML
Acronym
SOPRA
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

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
March 2014 (undefined)
Primary Completion Date
January 8, 2018 (Actual)
Study Completion Date
January 8, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Karyopharm Therapeutics Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)
Keywords
Relapsed/Refractory Acute Myeloid Leukemia, Acute Myeloid Leukemia, AML, Karyopharm, Selinexor, KPT-330

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
317 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Selinexor approximately 55 mg/m^2 (60 to 120 mg based on BSA)
Arm Type
Experimental
Arm Description
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).
Arm Title
Selinexor 60 mg (PV <5) (Equivalent to 35 mg/m^2)
Arm Type
Experimental
Arm Description
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).
Arm Title
Selinexor 60 mg (PV >=5) (Equivalent to 35 mg/m^2)
Arm Type
Experimental
Arm Description
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).
Arm Title
Physician's Choice 1 (PV <5)
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Physician's Choice 2 (PV >=5)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Selinexor
Other Intervention Name(s)
KPT-330
Intervention Description
Selinexor oral tablet.
Intervention Type
Drug
Intervention Name(s)
Hydroxyurea
Other Intervention Name(s)
Hydroxycarbamide
Intervention Type
Drug
Intervention Name(s)
Ara-C
Other Intervention Name(s)
Cytarabine, Cytosine arabinoside, Cytosar-U, Depocyt
Intervention Description
Ara-C Subcutaneous Injection.
Primary Outcome Measure Information:
Title
Overall Survival
Description
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.
Time Frame
Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Overall Survival of at Least 3 Months (OS3.0)
Description
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. Analysis was performed using Kaplan-Meier method.
Time Frame
From randomization (Day 1) up to 3 months
Title
Percentage of Participants With Complete Remission Rate (CRR) for Those Who Achieved Complete Remission (CR)
Description
CRR was analyzed using International Working Group (IWG) 2003 criteria, as the difference in the proportions of participants with IWG results of CR. CR per IWG 2003 criteria was defined as morphologic presence of < 5 percentage (%) myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood absolute neutrophil count (ANC) > 1000 cells/microliter (microL) and platelet count > 100,000/microL, with no need for red blood cell (RBC) transfusions), and the absence of extramedullary disease.
Time Frame
Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Title
Median Disease-Free Survival (DFS) for Participants Who Achieved Complete Remission (CR)
Description
DFS for CRR based on IWG criteria, was calculated from the first date of response of CR to the date of progression or recurrence, or date of death if progression or recurrence did not occur. Participants who discontinued prior to disease progression or recurrence or did not progress as of the time of the analysis were censored at the time of last radiologic assessment. CR per IWG 2003 criteria was defined as morphologic presence of < 5 % myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease.
Time Frame
Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Title
Percentage of Participants With Modified Complete Remission Rate (mCRR) for Those Who Achieved Complete Remission (CR) or Complete Remission With Incomplete Hematologic Recovery (Cri)
Description
mCRR was defined as the point estimate of the percentage of participants who had CR, CRi, or CRp. Responses defined as per IWG 2003 response criteria: Morphologic CR:< 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.
Time Frame
Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Title
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)
Description
DFS based on IWG criteria was defined as the duration from start of the complete response achieved until disease progression or death from any cause. Responses defined by IWG 2003 Response Criteria: Morphologic CR: < 5% myeloblasts in bone marrow, the absence of circulating blasts, hematologic recovery (as evidenced by a peripheral blood ANC > 1000 cells/microL and platelet count > 100,000/microL, with no need for RBC transfusions), and the absence of extramedullary disease. Morphologic CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), Cri (< 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]), normal maturation of all cellular components in the bone marrow, no extramedullary disease and transfusion independent.
Time Frame
Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Title
Percentage of Participants With Overall Response Rate (ORR)
Description
Overall response rate was defined as the point estimate of the percentage of participants who achieved CR (disappearance of all target and non-target lesions), partial response (PR) (>=30 % decrease in sum of longest diameters of target lesions taking as reference baseline sum longest diameters associated to non-progressive disease response for non-target lesions). CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. CRp; All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L) and morphologic leukemia-free state (MLFS); morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%, in absence of blasts with Auer rods, no hematologic recovery required.
Time Frame
Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Title
Duration of Response (DOR)
Description
DOR was calculated from date of response of CR, CRi, CRp, MLFS, or PR to date of progression or recurrence based on IWG criteria. CR: <5% myeloblasts in bone marrow,absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL, platelet count > 100,000/microL, no need for RBC transfusions), absence of extramedullary disease. PR: No circulating blasts, neutrophil count > =1.0 x10^9/L, platelet count >= 100 x10^9/L, >= 50 % reduction in bone marrow blast to 6% to 25%, or blasts less than or equal to (<=) 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1x10^9/L) or thrombocytopenia (<100 x10^9/L), CRi; < 5% bone marrow blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS: morphologic bone marrow blast clearance to < 5% in marrow sample, <= 200 cells enumerated/cellularity is ≥ 10%, in absence of blasts with Auer rods, no hematologic recovery required.
Time Frame
Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (up to a maximum of approximately 104 weeks)
Title
Percentage of Participants With Disease Control Rate (DCR)
Description
DCR:Point estimate of % of participants with CR,CRi,CRp,MLFS,PR, or SD for <=4 weeks.CR:<5% myeloblasts in bone marrow (BM),absence of circulating blasts,hematologic recovery(peripheral blood ANC >1000 cells/microL and platelet count >100,000/microL, no need of RBC transfusions),absence of extramedullary disease. PR:No circulating blasts,Neutrophil count >=1.0 x10^9/L, Platelet count >= 100*10^9/L, >=50% reduction in BM blast to 6% to 25%, or blasts <=5% if Auer rods are present.CRp:All criteria for CR except for residual neutropenia (<1*10^9/L) or thrombocytopenia(<100 x10^9/L),CRi;< 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS:morphologic BM blast clearance to <5% in a marrow sample in which <=200 cells enumerated or cellularity is ≥10%,in absence of blasts with Auer rods,no hematologic recovery required,SD:failure to achieve a response but not meeting criteria for disease progression over period of >4 weeks.
Time Frame
Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria
Title
Duration of Disease Control Rate
Description
Duration of DCR calculated for all participants with DCR. CR: < 5% myeloblasts in BM, absence of circulating blasts, hematologic recovery (peripheral blood ANC >1000 cells/microL and platelet count > 100,000/microL, no need for RBC transfusions), absence of extra medullary disease. PR: No circulating blasts, Neutrophil count >=1.0 x 10^9/L, Platelet count >= 100 x 10^9/L, >= 50 % reduction in BM blast to 6% to 25%, or blasts <= 5% if Auer rods are present. CRp: All criteria for CR except for residual neutropenia (<1 x 10^9/L) or thrombocytopenia (<100 x 10^9/L), CRi; < 5% BM blasts with residual neutropenia [ANC < 1000 cells/microL] or thrombocytopenia [platelets < 100,000/microL]. MLFS; morphologic BM blast clearance to < 5% in a marrow sample in which <=200 cells enumerated/cellularity is >= 10%, in absence of blasts with Auer rods, no hematologic recovery required and SD; failure to achieve a response but not meeting criteria for disease progression over period of > 4 weeks.
Time Frame
Up to 4 weeks from the date of randomization to the date of progression or recurrence based on IWG criteria
Title
Change From Baseline in Quality of Life (QoL) and Patient-Reported Outcomes (Functional Assessment of Cancer Therapy -Leukemia [FACT-Leu]
Description
QoL was assessed by the FACT-Leu. FACT-Leu combines the General version of the Functional Assessment of Cancer Therapy (FACT-G) with a leukemia-specific sub-scale (17 items). The sub-scales for the FACT-G are Physical Well-Being (7 items), Social/Family Well-Being (7 items), Emotional Well-Being (6 items), and Functional Well-Being (7 items). The trial outcomes index (TOI; total of 31 items) was the primary measurement of interest, comprising the Physical and Functional sub-scales plus the leukemia - specific sub-scale. Each item was rated on a 5-point Likert scale. Range from 0 = (Not at all) to 4 = (Very much); therefore, the TOI had a score ranging from 0 to 124. Higher scores indicated improvement in well being. The QoL assessment was performed at baseline (prior to first dose of study treatment), Day 1 of each cycle on or after the second, and at the final visit.
Time Frame
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)
Title
Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Health Questionnaire Visual Analogue Scale (VAS)
Description
EQ-5D descriptive system comprises of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1=no problems, 2=slight problems, 3=moderate problems, 4=severe problems, and 5=extreme problems. EQ-5D-5L is a standardized instrument that measures health-related quality of life for men with prostate cancer. EQ-5D consists of EQ-5D descriptive system and EQ VAS. EQ-5D-5-VAS records participant's self-rated health on a vertical VAS that allows them to indicate their health state that can range from 0 (worst imaginable) to 100 (best imaginable), higher scores indicating a better health state.
Time Frame
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)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
Jonsson Comprehensive Cancer Center / University of California, Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Facility Name
Sutter Oncology & Hematology
City
Sacramento
State/Province
California
ZIP/Postal Code
95816
Country
United States
Facility Name
Stanford Cancer Institute / Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Colorado Blood Cancer Institute/Sarah Cannon Research Institute
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Yale Cancer Center / Yale University
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
H. Lee Moffitt Cancer Center and Research Institute
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Winship Cancer Institute / Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
University of Chicago Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Kansas Hospital
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Sidney Kimmel Comprehensive Cancer Center / John Hopkins University
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Facility Name
University of Massachusetts Medical School
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-0944
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Westchester Medical Center / New York Medical College
City
Hawthorne
State/Province
New York
ZIP/Postal Code
10532
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
New York Presbyterian Hospital / Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
Duke Cancer Care
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Ohio State University Comprehensive Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Milton S. Hershey Medical Center / Penn State
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Tennessee Oncology/Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center / Vanderbilt University
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37215
Country
United States
Facility Name
MD Anderson Cancer Center / University of Texas
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Transplant Institute/Sarah Cannon Research Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Tom Baker Cancer Centre
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 4N2
Country
Canada
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2G3
Country
Canada
Facility Name
Sir Mortimer B. Davis Jewish General Hospital / McGill University
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H2W1S6
Country
Canada
Facility Name
Aarhus University Hospital
City
Aarhus
Country
Denmark
Facility Name
Department of Haematology, National University Hospital, Rigshospitalet
City
Copenhagen
Country
Denmark
Facility Name
Herlev Hospital
City
Herlev
Country
Denmark
Facility Name
Odense University Hospital, Department of Hematology
City
Odense
Country
Denmark
Facility Name
CHU Bordeaux- Hôpital Haut Lévêque
City
Bordeaux
Country
France
Facility Name
Centre Hospitalier Lyon
City
Lyon
Country
France
Facility Name
Hopital Saint Louis
City
Paris
Country
France
Facility Name
Hôpital Avicenne
City
Paris
Country
France
Facility Name
Institut Universitaire du Cancer Toulouse
City
Toulouse
Country
France
Facility Name
Stellvertretende Klinikleiterin Charité, Campus Benjamin Franklin
City
Berlin
ZIP/Postal Code
12203
Country
Germany
Facility Name
Ev. Diakonie-Krankenhaus Gemeinnutzige GMBH Medizinische Klinik 2
City
Bremen
Country
Germany
Facility Name
UNIVERSITÄTSKLINIKUM TU DRESDEN Medizinische Klinik und Poliklinik I,
City
Dresden
Country
Germany
Facility Name
University Hospital Frankfurt
City
Frankfurt
Country
Germany
Facility Name
Medizinische Hochschule Hannover (Hannover Medical School) Dept. of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation
City
Hanover
Country
Germany
Facility Name
Abteilung Hämatologie, internistische Onkologie und Hämostaseologie
City
Leipzig
Country
Germany
Facility Name
UNIVERSITY HOSPITAL OF MÜNSTER Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster
City
Münster
Country
Germany
Facility Name
Universitätsklinikum Ulm
City
ULM
Country
Germany
Facility Name
Sororka MC
City
Beer Sheva
ZIP/Postal Code
85025
Country
Israel
Facility Name
Rambam Health Care Campus
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Wolfson Medical Center
City
Holon
Country
Israel
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Rabin Medical Center
City
Petach Tikva
ZIP/Postal Code
4941492
Country
Israel
Facility Name
Tel Aviv Sourasky Medical Centre
City
Tel Aviv
Country
Israel
Facility Name
Chaim Sheba Medical Center
City
Tel Hashomer
ZIP/Postal Code
52621
Country
Israel
Facility Name
AOU Ospedali Riuniti di Ancona
City
Ancona
Country
Italy
Facility Name
A.O Spedali Civili di Brescia
City
Brescia
Country
Italy
Facility Name
AORN Cardarelli / UOSC di Ematologia con TMO
City
Naples
Country
Italy
Facility Name
AMC, Academisch Medisch Centrum Afdeling Klinische Hematologie
City
Amsterdam
Country
Netherlands
Facility Name
VU University Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
Universitair Medisch Centrum Groningen Department of Haematology
City
Groningen
Country
Netherlands
Facility Name
Radboud University Medical Center Department of Haematology (476)
City
Nijmegen
Country
Netherlands
Facility Name
Erasmus MC, location Daniel den Hoed
City
Rotterdam
Country
Netherlands
Facility Name
University Medical Center Utrecht
City
Utrecht
Country
Netherlands
Facility Name
Isala Kliniecken Zwolle
City
Zwolle
Country
Netherlands
Facility Name
Wojewódzki Szpital Specjalistyczny im. M. Kopernika, Klinika Hematologii
City
Lodz
Country
Poland
Facility Name
Samodzielny Publiczny Zakład Opieki Zdrowotnej Ministerstwa Spraw Wewnętrznych
City
Olsztyn
Country
Poland
Facility Name
Instytut Hematologii i Transfuzjologii
City
Warszawa
Country
Poland
Facility Name
Samodzielny Publiczny Szpital Kliniczny Nr 1 we Wrocławiu
City
Wroclaw
Country
Poland
Facility Name
ICO Badalona
City
Badalona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Hospital del Mar
City
Barcelona
Country
Spain
Facility Name
Hospital Universitario de Salamanca Servicio de Hematologia
City
Salamanca
Country
Spain
Facility Name
Hospital Universitario y Politécnico La Fe
City
Valencia
Country
Spain
Facility Name
Northwick Park Hospital
City
Harrow
State/Province
England
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
Facility Name
Royal Liverpool University Hospital, Dept of Cellular and Molecular Physiology, Molecular and Clinical Cancer Medicine
City
Liverpool
State/Province
Lancashire
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
Royal Marsden NHS Trust
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom
Facility Name
University Hospital Wales
City
Cardiff
State/Province
Wales
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
Hull and East Yorkshire Hospitals NHS Trust Queens Centre for Oncology and Haematology
City
Hull
State/Province
Yorkshire
ZIP/Postal Code
HU3 2JZ
Country
United Kingdom
Facility Name
Ninewells Hospital and Medical School NHS Tayside
City
Dundee
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
Facility Name
Plymouth Hospitals NHS Trust/Derriford Hospital
City
Plymouth
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
Citations:
PubMed Identifier
34323164
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.
Results Reference
derived

Learn more about this trial

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

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