Selinexor With Fludarabine and Cytarabine for Treatment of Refractory or Relapsed Leukemia or Myelodysplastic Syndrome

Summary

The purpose of this study is to test the safety of selinexor (KPT-330) and to find the highest dose of selinexor (KPT-330) that can be given safely when it is combined with two chemotherapy drugs (fludarabine and cytarabine). This study will be done in two parts: Phase I and Phase II.

The goal of Phase I is to find the highest tolerable dose of selinexor (KPT-330) that we can give to patients with leukemia or MDS, when it is combined with fludarabine and cytarabine.

The goal of the subsequent Phase II portion of the study (insert NCT ID of SELHEM-2) 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 leukemia or MDS. The investigators will examine the effect of this combination treatment.

PRIMARY OBJECTIVE:

* Determine a tolerable combination of selinexor, fludarabine, and cytarabine in pediatric patients with relapsed or refractory hematologic malignancies included acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), mixed phenotype acute leukemia (MPAL) and myelodysplastic syndrome (MDS).

SECONDARY OBJECTIVES:

* To characterize the pharmacokinetics of selinexor, when administered in tablet form, after the first dose and at steady-state, as well as in combination with fludarabine and cytarabine
* To estimate the overall response rate of selinexor given with fludarabine and cytarabine in patients with relapsed or refractory hematologic malignancies

Conditions

• Acute Myeloid Leukemia (AML)
• Acute Lymphoblastic Leukemia (ALL)
• Myelodysplastic Syndrome (MDS)
• Mixed Phenotype Acute Leukemia (MPAL)

Interventions

DRUG

Selinexor

Given orally on days 1,3,8,10,22 and 24 of each cycle

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.

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.

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).

Sponsors & Collaborators

• Karyopharm Therapeutics Inc

  collaborator INDUSTRY

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Jeffrey E. Rubnitz, MD,PhD · St. Jude Children's Research Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

24 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2014-08-31

Primary Completion

2015-12-31

Completion

2015-12-31

FDA Drug

Yes

Countries

• United States

Study Locations