Cytarabine and Daunorubicin Hydrochloride with or without Selinexor in Treating Older Patients with Acute Myeloid Leukemia

Status: Active

Description

This randomized phase II trial studies how well cytarabine and daunorubicin hydrochloride with or without selinexor work in treating older patients with acute myeloid leukemia. 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 may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving cytarabine and daunorubicin hydrochloride with selinexor may kill more cancer cells in older patients with acute myeloid leukemia.

Eligibility Criteria

Inclusion Criteria

  • Patients must have histologically or cytologically documented newly diagnosed de novo acute myeloid leukemia (non-acute promyelocytic leukemia [APL]) that has not yet been treated; hydrea and all-trans retinoic acid (ATRA) previous treatments are acceptable
  • Patients must not have a secondary acute myeloid leukemia (AML) (defined as a history of prior radiation therapy or systemic chemotherapy, antecedent myelodysplastic syndrome [MDS], myeloproliferative neoplasm [MPN] or chronic myelomonocytic leukemia [CMML])
  • Hydroxyurea may be used to control leukocytosis, provided that it is without grade > 2 toxicity, and can be taken until start of therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 2 and fit for induction therapy in the opinion of the treating physician
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
  • Bilirubin =< 2 X ULN (3 X if known history of Gilbert's syndrome)
  • Creatinine clearance (CrCl) must be > 20 mL/min
  • Baseline left ventricular ejection fraction of at least 40% by multigated acquisition (MUGA) or echocardiography (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 Institutional Review Board (IRB)-approved informed consent document

Exclusion Criteria

  • Patients who have received any therapy other than hydroxyurea or ATRA with the purpose of treating their AML or patients with acute promyelocytic leukemia are not eligible
  • Patients with a secondary AML (defined as a history of prior radiation therapy or systemic chemotherapy, antecedent MDS, MPN or CMML)
  • 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 central nervous system (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 human immunodeficiency virus (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 gastrointestinal (GI) disease or GI dysfunction that could interfere with absorption of study treatment
  • Prior exposure to a short interspersed element (SINE) compound

Locations & Contacts

North Carolina

Winston-Salem
Wake Forest University Health Sciences
Status: Active
Contact: Timothy S. Pardee
Phone: 336-716-5847
Email: tspardee@wakehealth.edu

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. To compare the overall survival of patients receiving the proposed study regimen versus standard of care (SOC) (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]) 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 versus (vs) SOC (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 SOC.

EXPLORATORY OBJECTIVES:

I. To obtain optional plasma and bone marrow samples for future research studies, the nature of which will be at the discretion of the study principal investigator (PI).

OUTLINE: Patients are randomized to 1 or 2 arms.

ARM I:

INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7 and daunorubicin hydrochloride IV on days 1-3. 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 and daunorubicin hydrochloride IV on days 1-2. 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 6. Treatment repeats every 42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

ARM II:

INDUCTION THERAPY: Patients receive cytarabine intravenously (IV) on days 1-7, selinexor orally (PO) on days 1, 3, 8, 10, 15, and 17, and daunorubicin hydrochloride IV on days 1-3. 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, selinexor PO on days 1, 3, 8, 10, 15, and 17, and daunorubicin hydrochloride IV on days 1-2. 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 6 and selinexor PO on days 1, 3, 8, 10, 15, and 17. Treatment repeats every 42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY: Patients who have had a response, completed all planned consolidation therapy, and have not gone on to transplant receive selinexor PO on days 1 and 8. Treatment continues for 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days and then every 3 months for up to 1 year.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Wake Forest University Health Sciences

Principal Investigator
Timothy S. Pardee

Trial IDs

Primary ID CCCWFU 22316
Secondary IDs NCI-2016-00951
Clinicaltrials.gov ID NCT02835222