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Trial record 1 of 1 for:    NCT02835222
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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 : February 17, 2020
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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
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 : October 2020
Estimated Study Completion Date : October 2020


Arm Intervention/treatment
Experimental: 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.

MAINTENANCE: Have had a response, completed all planned consolidation, have not gone to transplant receive selinexor on Days 1 and 8 for cycle 1 only, then Day 1 for cycles 2-4; Day 1 of every 4th cycle. Treatment continues until 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

Active Comparator: 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.

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




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


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. Progress-free survival [ Time Frame: Up to 1 year ]
    Kaplan-Meier survival analysis methods to compare time to progression.

  3. Rate of allogeneic stem cell transplantation [ Time Frame: Up to 1 year ]
    Fisher's exact tests to compare rates.

  4. Response rate of complete remission (CR) or complete remission with incomplete recovery (CRi) [ 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 de novo Acute Myeloid Leukemia (non-APL) that has not yet been treated. Hydrea and ATRA previous treatments are acceptable.
  • 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.
  • Hydroxyurea may be used to control leukocytosis, provided that it is without Grade >2 toxicity, and can be taken until start of therapy.
  • Age >60 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. Please refer to Section 6.4.4 of this protocol.
  • 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 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, 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

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
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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
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Principal Investigator: Timothy Pardee Wake Forest University Health Sciences

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT02835222    
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: February 17, 2020
Last Verified: February 2020

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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:
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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