Study of Selinexor and Venetoclax in Combination With Chemotherapy in Pediatric and Young Adult Patients With Refractory or Relapsed Acute Myeloid Leukemia

Summary

The purpose of this study is to test the safety and determine the best dose of venetoclax and selinexor when given with chemotherapy drugs in treating pediatric and young adult patients with acute myeloid leukemia (AML) or acute leukemia of ambiguous lineage (ALAL) that has come back (relapsed) or did not respond to treatment (refractory).

Primary Objective

* To determine the safety and tolerability of selinexor and venetoclax in combination with chemotherapy in pediatric patients with relapsed or refractory AML or ALAL.

Secondary Objectives

* Describe the rates of complete remission (CR) and complete remission with incomplete count recovery (CRi) for patients treated with selinexor and venetoclax in combination with chemotherapy at the recommended phase 2 dose (RP2D).
* Describe the overall survival of patients treated at the RP2D.

Exploratory Objectives

* Explore associations between leukemia cell genomics, BCL2 family member protein quantification, BH3 profiling, and response to therapy as assessed by minimal residual disease (MRD) and variant clearance using cell-free deoxyribonucleic acid (DNA) (cfDNA).
* Describe the quality of life of pediatric patients undergoing treatment with selinexor and venetoclax in combination with chemotherapy and explore associations of clinical factors with patient-reported quality of life outcomes.
* Describe the clinical and genetic features associated with exceptional response to the combination of venetoclax and selinexor without the addition of chemotherapy.

Conditions

• Acute Leukemia of Ambiguous Lineage in Relapse
• Acute Myeloid Leukemia, in Relapse
• Refractory Acute Leukemia of Ambiguous Lineage
• Refractory Acute Myeloid Leukemia

Interventions

DRUG

Venetoclax

Given orally (PO)

DRUG

Selinexor

Given Orally (PO)

DRUG

Cytarabine

Given in to the vein (IV) or intrathecal (IT)

DRUG

Fludarabine

Given in to the vein (IV) - Because of the ongoing nationwide shortage of fludarabine, this agent may be omitted during the dose expansion phase of the trial.

BIOLOGICAL

Filgrastim

Given subcutaneous (SubQ, SC)

DRUG

Methotrexate

Given intrathecal (IT)

DRUG

methotrexate/hydrocortisone/cytarabine

Given intrathecal (IT)

Sponsors & Collaborators

• Karyopharm Therapeutics Inc

  collaborator INDUSTRY

• AbbVie

  collaborator INDUSTRY

• Gateway for Cancer Research

  collaborator OTHER

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Seth Karol, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

2 Years

Max Age

30 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-11-15

Primary Completion

2023-07-12

Completion

2027-09-30

FDA Drug

Yes

Countries

• United States

Study Locations