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
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|
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.
- 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)|
|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|
Experimental: Treatment Arm
Interventions: Selinexor, Fludarabine, and Cytarabine. Methotrexate/hydrocortisone/cytarabine (intrathecal triples) will be given prior to cycle 1.
Given orally on days 1,3,8,10,22 and 24 of each cycle
Other Name: KPT-330
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.
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.
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).
- 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.
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
|Contact: Jeffrey E. Rubnitz, MD,PhDfirstname.lastname@example.org|
|United States, Arizona|
|Phoenix Children's Hospital||Recruiting|
|Phoenix, Arizona, United States, 85016|
|Contact: Jessica Boklan, MD 602-933-0920 email@example.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 firstname.lastname@example.org|
|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 email@example.com|
|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 firstname.lastname@example.org|
|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 email@example.com|
|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 firstname.lastname@example.org|
|Principal Investigator: Kenneth M. Heym, MD|
|Principal Investigator:||Jeffrey E. Rubnitz, MD,PhD||St. Jude Children's Research Hospital|