NCT02299518

Selinexor and Chemotherapy in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Phase 1 Study of Selinexor in Combination With Topoisomerase-II Inhibition in Acute Myeloid Leukemia

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 23 (actual)
• Sponsor: Alice Mims · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of selinexor when given together with etoposide with or without mitoxantrone hydrochloride and cytarabine in treating patients with acute myeloid leukemia that has returned (relapsed) or has not responded to treatment (refractory). Selinexor may help stop the growth of tumor cells by blocking an enzyme needed for cancer cell growth. Drugs used in chemotherapy, such as etoposide, mitoxantrone hydrochloride, and cytarabine, 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. Giving chemotherapy together with selinexor work better in treating relapsed or refractory acute myeloid leukemia.

Detailed description

PRIMARY OBJECTIVES: I. To evaluate the safety and tolerability of selinexor in combination with mitoxantrone hydrochloride, etoposide, cytarabine (MEC) or oral etoposide (respective cohorts are independent of each other) in patients with relapsed or refractory acute myeloid leukemia (AML). II. To define the specific toxicities, maximum tolerated dose (MTD) and the dose limiting toxicities (DLT) of these combinations. III. To determine the recommended phase 2 dose (RP2D) of these combinations. SECONDARY OBJECTIVES: I. To determine the rate and duration of complete remission (CR) ± hematologic recovery of selinexor plus MEC therapy in AML. II. To determine the overall response rate (ORR). III. To define the rate of complete remission (CR + CR with incomplete blood count recovery \[CRi\]) rate by the end of induction therapy. IV. Determine the disease-free survival for patients who reached CR/CRi within 1 year. TERTIARY OBJECTIVES: I. To conduct pharmacodynamic studies by measuring the effect of these chemotherapy combinations on the inhibition of exportin 1 (XPO1). II. To conduct pharmacokinetic sampling of selinexor and etoposide at limited time points to assess drug metabolism, peak plasma levels and area under curve (AUC). OUTLINE: This is a dose-escalation study of selinexor. Patients are assigned to 1 of 2 cohorts. COHORT A (PATIENTS FIT FOR INTENSIVE THERAPY, AGE \< 60): Patients receive mitoxantrone hydrochloride intravenously (IV), etoposide IV, and cytarabine IV once daily (QD) on days 1-6 and selinexor orally (PO) on days 1, 3, 8, 10, 15, and 17. Treatment continues for 1 course (28 days). Further treatment is based on disease response. Patients achieving CR/CRi are evaluated for stem cell transplant; patients who do not proceed to transplant may receive selinexor as monotherapy in the absence of disease progression or unacceptable toxicity. COHORT B (PATIENTS UNFIT FOR INTENSIVE THERAPY, AGE ≥ 60): Patients receive etoposide PO QD on days 1-5 and selinexor PO on days 1, 3, 8, 10, 15, and 17. Treatment may repeat every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients not achieving response after 4 courses discontinue treatment; patients achieving response may receive up to 4 courses of maintenance therapy every 8 weeks. Patients may then continue selinexor as monotherapy at the discretion of the principal investigator. After completion of study treatment, patients are followed up for at least 30 days.

Conditions

• Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
• Adult Acute Myeloid Leukemia With Del(5q)
• Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)
• Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
• Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
• Recurrent Adult Acute Myeloid Leukemia
• Secondary Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	mitoxantrone hydrochloride	Given IV
DRUG	etoposide	Given IV and PO
DRUG	cytarabine	Given IV
DRUG	selinexor	Given PO
OTHER	laboratory biomarker analysis	Correlative studies
OTHER	pharmacological study	Correlative studies

Timeline

• Start date: 2015-05-18
• Primary completion: 2018-03-06
• Completion: 2018-03-06
• First posted: 2014-11-24
• Last updated: 2023-06-15

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study