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Selinexor With Induction, Consolidation, and Maintenance Therapy in Treating Older Patients With Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT02835222
Recruitment Status : Recruiting
First Posted : July 18, 2016
Last Update Posted : July 16, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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.

Condition or disease Intervention/treatment Phase
Untreated Adult Acute Myeloid Leukemia Drug: Cytarabine Drug: Daunorubicin Hydrochloride Drug: Selinexor Phase 2

Detailed Description:

PRIMARY OBJECTIVES:

I. Assess the feasibility of adding selinexor to induction, consolidation and maintenance therapy of elderly acute myeloid leukemia (AML) patients.

SECONDARY OBJECTIVES:

I. To assess the safety of administering selinexor under the proposed study regimen.

II. To assess response and survival endpoints of patients receiving the proposed study regimen.

III. To assess the rate of allogeneic stem cell transplantation.

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 6, 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.

MAINTENANCE THERAPY: Patients who have had a response and have not gone on to transplant receive selinexor PO twice weekly. Treatment continues for 4 weeks 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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Phase II Study of Selinexor in Combination With Induction/Consolidation/Maintenance Therapy in Older AML Patients
Actual Study Start Date : February 2, 2018
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2020


Arm Intervention/treatment
Experimental: cytarabine, daunorubicin, 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: 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: Patients in remission receive cytarabine IV every 12 hours on days 1, 3 and 6, 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.

MAINTENANCE THERAPY: Patients who have had a response and have not gone on to transplant receive selinexor PO twice weekly. Treatment continues for 4 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Cytarabine
Given IV
Other Names:
  • .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

Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • Cloridrato de Daunorubicina
  • Daunoblastin
  • Daunoblastina
  • Daunoblastine
  • Daunomycin Hydrochloride
  • Daunomycin, hydrochloride
  • Daunorubicin.HCl
  • Daunorubicini Hydrochloridum
  • FI-6339
  • Ondena
  • RP-13057
  • Rubidomycin Hydrochloride
  • Rubilem

Drug: Selinexor
Given PO
Other Names:
  • CRM1 Nuclear Export Inhibitor KPT-330
  • KPT-330
  • Selective Inhibitor of Nuclear Export KPT-330
  • SINE KPT-330




Primary Outcome Measures :
  1. Feasibility of combining selinexor with induction/consolidation/maintenance therapy assessed by percentage of patients eligible for maintenance therapy who complete at least 3 courses [ Time Frame: Up to 1 year ]

Secondary Outcome Measures :
  1. Incidence of adverse events assessed by Common Terminology Criteria for Adverse Events version 4.0 [ Time Frame: Up to 1 year ]
    The frequency of toxicities experienced by the participants will be presented by type and grade in an effort to monitor and report safety of the treatment.

  2. Overall survival [ Time Frame: Up to 1 year ]
    Kaplan-Meier estimation will be used to analyze the overall survival.

  3. Progress-free survival [ Time Frame: Up to 1 year ]
  4. Rate of allogeneic stem cell transplantation [ Time Frame: Up to 1 year ]
  5. Rate of complete remission [ Time Frame: Up to 1 year ]
    Confidence intervals will be calculated around the estimates of the response rate (complete remission and complete remission with incomplete recovery).



Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically documented newly diagnosed 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
  • Hydroxyurea may be used to control leukocytosis and can be taken until start of therapy
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 3 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 =< 2 mg/dL
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • 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 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
  • 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, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with known human immunodeficiency virus (HIV) infection
  • Pregnant women are excluded from this study; breastfeeding should be discontinued

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02835222


Locations
United States, North Carolina
Comprehensive Cancer Center of Wake Forest University Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Timothy S. Pardee    336-716-5847    tspardee@wakehealth.edu   
Principal Investigator: Timothy S. Pardee         
Sponsors and Collaborators
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Investigators
Principal Investigator: Timothy Pardee Wake Forest University Health Sciences

Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT02835222     History of Changes
Other Study ID Numbers: IRB00039092
NCI-2016-00951 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CCCWFU 22316 ( Other Identifier: Comprehensive Cancer Center of Wake Forest University )
P30CA012197 ( U.S. NIH Grant/Contract )
First Posted: July 18, 2016    Key Record Dates
Last Update Posted: July 16, 2018
Last Verified: July 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors