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Trial record 1 of 1 for:    NCT03071276
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Selinexor in Combination With Fludarabine and Cytarabine in Patients With Refractory or Relapsed Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT03071276
Recruitment Status : Recruiting
First Posted : March 6, 2017
Last Update Posted : October 10, 2018
Sponsor:
Collaborator:
Karyopharm Therapeutics Inc
Information provided by (Responsible Party):
St. Jude Children's Research Hospital

Brief Summary:

This study will be done in two parts: Phase I (NCT02212561) has been completed and published. The goal of the Phase I portion of this study was to find the highest tolerable dose of selinexor (KPT-330) that can be given to patients with leukemia or myelodysplastic syndrome (MDS), when it is combined with fludarabine and cytarabine.

The Phase II portion of the protocol is reflected in this registration.

The goal of the Phase II portion of this protocol is to give the highest dose of selinexor (KPT-330) in combination with fludarabine/cytarabine that was found in Phase I to be safe for children with acute myeloid leukemia (AML). The investigators will examine the effect of this combination treatment.


Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (AML) Drug: Selinexor Drug: Fludarabine Drug: Cytarabine Drug: methotrexate/hydrocortisone/cytarabine Phase 2

Detailed Description:

After the recommended Phase II dose was determined, additional patients began enrolling to receive selinexor at the recommended dose level for further evaluation of tolerability and response.

PRIMARY OBJECTIVE:

  • To estimate the overall response rate, as defined by complete response or complete response with incomplete count recovery, of selinexor in combination with fludarabine and cytarabine for patients with relapsed or refractory AML in the phase II portion of the study.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 39 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II Study of the Selective Inhibitor of Nuclear Export Selinexor (KPT-330) in Combination With Fludarabine and Cytarabine in Patients With Refractory or Relapsed Leukemia or Myelodysplastic Syndrome
Actual Study Start Date : January 14, 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2019


Arm Intervention/treatment
Experimental: Treatment Arm
Interventions: Selinexor, Fludarabine, and Cytarabine. Methotrexate/hydrocortisone/cytarabine (intrathecal triples) will be given prior to cycle 1.
Drug: Selinexor
Given orally on days 1,3,8,10,22 and 24 of each cycle
Other Name: KPT-330

Drug: Fludarabine
Will be given intravenously (IV) over 30 minutes daily on days 16 through 20. Fludarabine may be given prior to day 16 if it is determined to be in the participant's best interest based on disease progression. Chemotherapy may be delayed by 1-3 days if clinically indicated.
Other Names:
  • Fludara®
  • Fludarabine phosphate
  • 2-fluoro-ara-AMP

Drug: Cytarabine
Will be given IV over 4 hours daily on days 16 through 20. Cytarabine may be given prior to day 16 if it is determined to be in the participant's best interest based on disease progression. Chemotherapy may be delayed by 1-3 days if clinically indicated.
Other Names:
  • Cytosine arabinoside
  • Ara-C
  • Cytosar®

Drug: methotrexate/hydrocortisone/cytarabine
Intrathecal (IT) triples will be given prior to cycle 1: IT cytarabine, IT methotrexate, and IT methotrexate/hydrocortisone/cytarabine (MHA) are acceptable. Patients without evidence of central nervous system (CNS) leukemia will receive no further IT therapy during cycle 1. Patients with CNS disease will receive weekly ITMHA until the cerebrospinal fluid becomes free of leukemia (minimum of 4 doses).
Other Names:
  • ITMHA
  • Intrathecal triples




Primary Outcome Measures :
  1. Overall Response Rate [ Time Frame: Between days 28 and 35 of cycle 1 (cycle length is 42-56 days) ]
    The efficacy of the combination of selinexor, fludarabine, and cytarabine, as measured by the complete response (CR) rate and the overall response (OR) rate (CR + CRi + PR) will be assessed for the patients enrolled at the MTD. The rates of CR and OR will be presented as a point estimate with a 95% exact binomial confidence interval.



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Ages Eligible for Study:   up to 24 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants must have a diagnosis of AML and must have disease that has relapsed or is refractory to chemotherapy, or that has relapsed after hematopoietic stem cell transplantation (HSCT)

    • Refractory disease is defined as persistent disease after at least two courses of induction chemotherapy.
    • Patients are eligible at first or subsequent relapse, whereas patients with ALL are eligible at second or subsequent relapse or any relapse that is refractory to salvage chemotherapy.
    • Patients must have ≥ 5% leukemic blasts in the bone marrow and/or increasing levels of MRD in the bone marrow as assessed by flow cytometry. If an adequate bone marrow sample cannot be obtained, patients may be enrolled if there is unequivocal evidence of leukemia in the peripheral blood.
  • Adequate organ function defined as the following:

    • Direct bilirubin ≤ 1.5 x institutional upper limit of normal (IULN)
    • AST (SGOT)/ALT (SGPT) < 3 x IULN
    • Creatinine within normal institutional limits for age
  • Prothrombin time (PT) and partial thromboplastin (PTT) ≤ 1.5 x IULN.
  • Age criteria: Patients treated at collaborating sites and current St. Jude patients who are on therapy or within 3 years of completion of therapy must be ≤ 24 years old. All other St. Jude patients must be < 21 years old.
  • Patients must be able to swallow tablets.
  • Performance status: Lansky ≥ 50 for patients who are ≤ 16 years old and Karnofsky ≥ 50% for patients who are > 16 years old.
  • Patients must have fully recovered from the acute effects of all prior therapy.
  • For patients who have received prior HSCT, there can be no evidence of GVHD and greater than 60 days must have elapsed since the HSCT.

Exclusion Criteria:

  • History of cerebellar toxicity or cerebellar neurological findings on exam.
  • Must not be pregnant or breastfeeding. Female patients of child-bearing potential must agree to use dual methods of contraception and have a negative serum pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for three months following the last dose.
  • Patients with Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or other bone marrow failure syndromes are not eligible.
  • Use of investigational agents, with the exception of gemtuzumab ozogamicin, within 30 days.
  • Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, study participation, follow up, or interpretation of study research.
  • Unstable cardiovascular function:

    • symptomatic ischemia
    • congestive heart failure NYHA Class > 3
    • myocardial infarction (MI) within 3 months
  • Uncontrolled infection requiring parenteral antibiotics, antivirals, or antifungals within one week prior to first dose. Infections controlled on concurrent anti-microbial agents are acceptable, and anti-microbial prophylaxis per institutional guidelines are acceptable.
  • Known human immunodeficiency virus (HIV) infection (pre-study testing not required).
  • Patients with malabsorption syndrome, or any other disease significantly affecting gastrointestinal function.
  • Prior treatment with selinexor.

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): NCT03071276


Contacts
Contact: Jeffrey E. Rubnitz, MD,PhD 866-278-5833 referralinfo@stjude.org

Locations
United States, Arizona
Phoenix Children's Hospital Recruiting
Phoenix, Arizona, United States, 85016
Contact: Jessica Boklan, MD    602-933-0920    jboklan@phoenixchildrens.com   
Principal Investigator: Jessica Boklan, MD         
United States, California
Lucile Packard Children's Hospital Stanford University Recruiting
Palo Alto, California, United States, 94304
Contact: Norman J. Lacayo, MD    650-497-8953    lacayon@stanford.edu   
Principal Investigator: Normal J. Lacayo, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Jennifer McNeer, MD    773-834-7424    jmcneer@peds.uchicago.edu   
Principal Investigator: Jennifer McNeer, MD         
United States, Michigan
Children's Hospital of Michigan Recruiting
Detroit, Michigan, United States, 48201
Contact: Jeffrey W. Taub, MD    313-745-5515    jtaub@med.wayne.edu   
Principal Investigator: Jeffrey W. Taub, MD         
United States, North Carolina
Duke University Medical Center Completed
Durham, North Carolina, United States, 27710
United States, Tennessee
St. Jude Children's Research Hospital Recruiting
Memphis, Tennessee, United States, 38105
Contact: Jeffrey E. Rubnitz, MD, PhD    866-278-5833    referralinfo@stjude.org   
Principal Investigator: Jeffrey E. Rubnitz, MD, PhD         
United States, Texas
Cook Children's Medical Center Recruiting
Fort Worth, Texas, United States, 76104
Contact: Kenneth M. Heym, MD    682-885-4007    kenneth.heym@cookchildrens.org   
Principal Investigator: Kenneth M. Heym, MD         
Sponsors and Collaborators
St. Jude Children's Research Hospital
Karyopharm Therapeutics Inc
Investigators
Principal Investigator: Jeffrey E. Rubnitz, MD,PhD St. Jude Children's Research Hospital

Additional Information:
Publications of Results:
Responsible Party: St. Jude Children's Research Hospital
ClinicalTrials.gov Identifier: NCT03071276     History of Changes
Other Study ID Numbers: SELHEM-2
NCI-2014-01704 ( Registry Identifier: NCI Clinical Trial Registration Program )
First Posted: March 6, 2017    Key Record Dates
Last Update Posted: October 10, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Methotrexate
Fludarabine phosphate
Cytarabine
Vidarabine
Fludarabine
Hydrocortisone 17-butyrate 21-propionate
Hydrocortisone acetate
Cortisol succinate
Hydrocortisone
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Antiviral Agents