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

Karyopharm Therapeutics

Status and phase: Completed; Phase 2

Conditions: Acute Myeloid Leukemia (AML)

Treatments: Drug: Ara-C; Drug: Hydroxyurea; Drug: Selinexor

Study type: Interventional

Funder types: Industry

Identifiers

NCT02088541

KCP-330-008

Details and patient eligibility

About

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.

Full 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.

Enrollment: 317 patients

Sex: All

Ages: 60+ years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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317 participants in 5 patient groups

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

Experimental group

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).

Treatment:

Drug: Selinexor

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

Experimental group

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).

Treatment:

Drug: Selinexor

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

Experimental group

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).

Treatment:

Drug: Selinexor

Physician's Choice 1 (PV <5)

Active Comparator group

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.

Treatment:

Drug: Hydroxyurea

Physician's Choice 2 (PV >=5)

Active Comparator group

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.

Treatment:

Drug: Ara-C