Selinexor With Combination With Induction/Consolidation Therapy in Acute Myeloid Leukemia Patients
An Investigator-Sponsored Randomized Phase II Study of Selinexor in Combination With Induction/Consolidation Therapy in Acute Myeloid Leukemia Patients
4 other identifiers
interventional
57
1 country
2
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Feb 2018
Longer than P75 for phase_2
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 7, 2016
CompletedFirst Posted
Study publicly available on registry
July 18, 2016
CompletedStudy Start
First participant enrolled
February 2, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 26, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 26, 2027
March 6, 2026
March 1, 2026
9.1 years
July 7, 2016
March 5, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Overall survival
Kaplan-Meier estimation will be used to analyze the overall survival. Overall survival (OS) is measured from the date of randomization to the date of death due to any cause. Participants will be monitored for survival through routine follow-up visits.
Up to 1 year
Secondary Outcomes (4)
Response rate of complete remission (CR) or complete remission with incomplete recovery (CRi)
Up to 1 year
Progression-free survival
Up to 1 year
Rate of allogeneic stem cell transplantation
Up to 1 year
Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events version 4.0
Up to 1 year
Study Arms (2)
Arm 2 (Selinexor) cytarabine, daunorubicin and selinexor
EXPERIMENTALINDUCTION: 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.
Standard of Care - Cytarabine and daunorubicin
ACTIVE COMPARATORINDUCTION: 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.
Interventions
Given IV
Given IV
Given PO
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Comprehensive Cancer Center of Wake Forest University
Winston-Salem, North Carolina, 27157, United States
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, 23298, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Timothy Pardee
Wake Forest University Health Sciences
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 7, 2016
First Posted
July 18, 2016
Study Start
February 2, 2018
Primary Completion (Estimated)
February 26, 2027
Study Completion (Estimated)
February 26, 2027
Last Updated
March 6, 2026
Record last verified: 2026-03