RECRUITING

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

An Investigator-Sponsored Randomized Phase II Study of Selinexor in Combination With Induction/Consolidation Therapy in Acute Myeloid Leukemia Patients

Quick Facts

Study Start:2018-02-02

Study Completion:2025-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT02835222

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patients must have histologically or cytologically documented newly diagnosed de novo Acute Myeloid Leukemia (non-APL) that has not yet been treated. Hydrea 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. * Patients ≤60 years of age must not have mutated FLT3 (either ITD OR TKD mutations). For patients \>60 years of age FLT3 status is not required to be known and if older than 60 years of age FLT3 mutated patients are eligible. * Hydroxyurea 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.	* Patients who have received any therapy other than hydroxyurea 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

Inclusion Criteria

Exclusion Criteria

* Patients must have histologically or cytologically documented newly diagnosed de novo Acute Myeloid Leukemia (non-APL) that has not yet been treated. Hydrea 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.
* Patients ≤60 years of age must not have mutated FLT3 (either ITD OR TKD mutations). For patients \>60 years of age FLT3 status is not required to be known and if older than 60 years of age FLT3 mutated patients are eligible.
* Hydroxyurea 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.

* Patients who have received any therapy other than hydroxyurea 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

Contacts and Locations

Study Contact

Study Coordinator

CONTACT

336-713-5878

dfunes@wakehealth.edu

Principal Investigator

Timothy Pardee

PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Study Locations (Sites)

Comprehensive Cancer Center of Wake Forest University

Winston-Salem, North Carolina, 27157

United States

Collaborators and Investigators

Sponsor: Wake Forest University Health Sciences

Timothy Pardee, PRINCIPAL_INVESTIGATOR, Wake Forest University Health Sciences

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2018-02-02

Study Completion Date2025-06

Study Record Updates

Study Start Date2018-02-02

Study Completion Date2025-06

Terms related to this study

Additional Relevant MeSH Terms

Untreated Adult Acute Myeloid Leukemia