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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

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

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

NCT ID

NCT02088541

First Posted

March 9, 2014

Last Updated

January 24, 2023

Sponsor

Karyopharm Therapeutics Inc

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

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

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

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

Arm Type

Experimental

Arm Description

Arm Title

Physician's Choice 1 (PV <5)

Arm Type

Active Comparator

Arm Description

Arm Title

Physician's Choice 2 (PV >=5)

Arm Type

Active Comparator

Arm Description

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

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

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

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

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

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

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

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

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

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

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

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

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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