Trial Search Results
Selinexor With Fludarabine and Cytarabine for Treatment of Refractory or Relapsed Leukemia or Myelodysplastic Syndrome
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.
- 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).
- 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
Stanford is currently not accepting patients for this trial.
St. Jude Children's Research Hospital
Collaborator: Karyopharm Therapeutics Inc
- Drug: Selinexor
- Drug: Fludarabine
- Drug: Cytarabine
- Drug: methotrexate/hydrocortisone/cytarabine
- Participants must have a diagnosis of AML, MDS, ALL or MPAL 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
- Patients with AML, MPAL or MDS 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 with AML or ALL must have ≥ 5% leukemic blasts in the bone marrow 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.
- 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
- 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
- Prior treatment with selinexor.
Ages Eligible for Study
N/A - 24 Years
Genders Eligible for Study