Selinexor With Combination With Induction/Consolidation Therapy in Acute Myeloid Leukemia Patients

NCT ID: NCT02835222

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

64 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-02-02

Study Completion Date

2026-03-31

Brief Summary

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This pilot phase II trial studies how well selinexor works when given together with induction, consolidation, and maintenance therapy in treating older patients with acute myeloid leukemia. Selinexor may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine and daunorubicin hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Selinexor with induction, consolidation, and maintenance therapy may kill more cancer cells in older patients with acute myeloid leukemia.

Detailed Description

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PRIMARY OBJECTIVES:

I. To compare the overall survival of patients receiving the proposed study regimen versus standard of care (defined as time from randomization to death from any cause).

SECONDARY OBJECTIVES:

I. To compare the response rate (Complete remission (CR), complete remission with incomplete count recovery (CRi) as per Dhoner et. al.) of patients receiving the proposed study regimen versus standard of care (SOC).

II To compare disease free survival in patients receiving the proposed study regimen vs standard of care (defined as time from randomization to relapse or death from any cause).

III. To assess the rate of allogeneic stem cell transplantation

IV. To compare the toxicity of the proposed study regimen vs standard of care.

OUTLINE:

INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7, daunorubicin hydrochloride IV on days 1-3, and selinexor orally (PO) twice weekly from day 1. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

RE-INDUCTION THERAPY: Patients whose disease has not responded receive cytarabine IV on days 1-5, daunorubicin hydrochloride IV on days 1-2, and selinexor PO twice weekly. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: Patients in remission receive cytarabine IV every 12 hours on days 1-3, and selinexor PO twice weekly from day 1. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 14 days and then every 3 months for up to 1 year.

Conditions

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Untreated Adult Acute Myeloid Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 2 (Selinexor) cytarabine, daunorubicin and selinexor

INDUCTION: Cytarabine IV on days 1-7, daunorubicin hydrochloride IV on days 1-3, and selinexor PO twice weekly from day 1. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

RE-INDUCTION: Disease has not responded receive cytarabine IV on days 1-5, daunorubicin hydrochloride IV on days 1-2, and selinexor PO twice weekly. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: In remission receive cytarabine IV every 12 hours for a total 6 doses days 1-3, and selinexor PO twice weekly from day 1. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Group Type EXPERIMENTAL

Cytarabine

Intervention Type DRUG

Given IV

Daunorubicin Hydrochloride

Intervention Type DRUG

Given IV

Selinexor

Intervention Type DRUG

Given PO

Standard of Care - Cytarabine and daunorubicin

INDUCTION: Cytarabine IV on days 1-7, daunorubicin hydrochloride IV on days 1-3. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

RE-INDUCTION: Disease has not responded receive cytarabine IV on days 1-5, daunorubicin hydrochloride IV on days 1-2. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION: In remission receive cytarabine IV every 12 hours for a total 6 doses days 1-3. Treatment repeats every 42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Group Type ACTIVE_COMPARATOR

Cytarabine

Intervention Type DRUG

Given IV

Daunorubicin Hydrochloride

Intervention Type DRUG

Given IV

Interventions

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Cytarabine

Given IV

Intervention Type DRUG

Daunorubicin Hydrochloride

Given IV

Intervention Type DRUG

Selinexor

Given PO

Intervention Type DRUG

Other Intervention Names

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SINE KPT-330 .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta-D-arabinofuranosylcytosine 1.beta.-D-Arabinofuranosylcytosine 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl- 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl- Alexan Ara-C ARA-cell Arabine Arabinofuranosylcytosine Arabinosylcytosine Aracytidine Aracytin Aracytine Beta-Cytosine Arabinoside CHX-3311 Cytarabinum Cytarbel Cytosar Cytosar-U Cytosine Arabinoside Cytosine-.beta.-arabinoside Cytosine-beta-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 Cerubidin Cerubidine Cloridrato de Daunorubicina Daunoblastin Daunoblastina Daunoblastine Daunomycin Hydrochloride Daunomycin, hydrochloride Daunorubicin.HCl Daunorubicini Hydrochloridum FI-6339 Ondena RP-13057 Rubidomycin Hydrochloride Rubilem CRM1 Nuclear Export Inhibitor KPT-330 KPT-330 Selective Inhibitor of Nuclear Export KPT-330

Eligibility Criteria

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Inclusion Criteria

* Patients must have histologically or cytologically documented newly diagnosed de novo Acute Myeloid Leukemia (non-APL) that has not yet been treated. Hydrea,cytarabine and ATRA previous treatments are acceptable.
* Patients with core binding factor acute myeloid leukemia (AML) (ie AML with t(8;21) or t(16;16) or i16) are not eligible.
* Patients must not have a secondary AML (defined as a history of prior radiation therapy or systemic chemotherapy, CMML or MDS not treated with a hypomethylating agent) however history of previous MDS treated with a hypomethylating agent IS allowed.
* Patients with de novo AML must not have partial or total monosomy 5 or 7 or i(17q) or t(17p). Negative FISH studies are sufficient for enrollment (i.e. FISH for -5, -7, +8, inv(16), t(8;21) and 17p).
* Patients must not have mutated FLT3 (either ITD OR TKD mutations).
* Hydroxyurea, leukapheresis or cytarabine may be used to control leukocytosis, provided that it is without Grade \>2 non-hematologic toxicity, and can be taken until start of therapy.
* Age \>18 years.
* ECOG performance status of ≤ 2 and fit for induction therapy in the opinion of the treating physician.
* Laboratory values ≤2 weeks must be:
* AST(SGOT)/ALT(SGPT)≤ 2.5 X institutional upper limit of normal
* Bilirubin ≤ 2 X ULN (3X if known history of Gilbert'syndrome)
* Creatinine clearance (CrCl) must be \> 20 mL/min
* Baseline left ventricular ejection fraction of at least 40% by MUGA or ECHO.
* Female patients of childbearing potential must agree to use 2 methods of contraception (including 1 highly effective and 1 effective method of contraception) and have a negative serum pregnancy test at Screening. Male patients must use an effective barrier method of contraception if sexually active with a female of childbearing potential. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose of study treatment.
* Ability to understand and the willingness to sign an IRB-approved informed consent document.

Exclusion Criteria

* Patients who have received any therapy other than hydroxyurea, cytarabine or ATRA with the purpose of treating their AML or patients with core binding factor AML or Acute Promyelocytic Leukemia are not eligible.
* Patients with a secondary AML (defined as a history of prior radiation therapy or systemic chemotherapy, CMML or MDS not treated with a hypomethylating agent) however history of previous MDS treated with a hypomethylating agent IS allowed.
* Patients having received prior radiotherapy, treatment with cytotoxic agents, treatment with biologic agents or any anti-cancer therapy for a non-AML malignancy within the 4 weeks prior to treatment with selinexor, or those who have not fully recovered from the acute, non-hematological, non-infectious toxicities of any prior treatment with cytotoxic drugs, radiotherapy or other anti-cancer modalities (returned to baseline status as noted before most recent treatment).
* Patients with another active malignancy that requires treatment excluding non-melanoma skin cancers.
* Patients that have received a chemotherapy regimen with stem cell support in the previous 6 months.
* Patients with known central nervous system involvement should be excluded from this clinical trial because the penetration of selinexor into the CNS is not currently known.
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to selinexor.
* Uncontrolled concurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
* Psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with known HIV infection or hepatitis (Note: Patients with known HIV infection are excluded because patients with an immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy.
* Pregnant women are excluded from this study because of the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother, breastfeeding should be discontinued.
* Patients unable to swallow tablets, patients with malabsorption syndrome, or any other GI disease or GI dysfunction that could interfere with absorption of study treatment
* Prior exposure to a SINE compound
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Timothy Pardee

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

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Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Study Coordinator

Role: CONTACT

Phone: 336-713-5878

Email: [email protected]

Facility Contacts

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Study Coordinator

Role: primary

Study Coordinator

Role: primary

Other Identifiers

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NCI-2016-00951

Identifier Type: REGISTRY

Identifier Source: secondary_id

CCCWFU 22316

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA012197

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00039092

Identifier Type: -

Identifier Source: org_study_id