SELCLAX: A Study of Venetoclax and Selinexor with Chemotherapy in Children with AML

Brief Summary

SELCLAX is a phase 1 study with an expansion cohort to evaluate the combination of venetoclax and selinexor plus chemotherapy in children with relapsed or refractory acute myeloid leukemia or acute leukemia of ambiguous lineage.

In previous studies, researchers have shown that each of these drugs is safe and active when combined with chemotherapy in children with relapsed or refractory AML. However, many patients do not respond to these regimens.

Preclinical data suggest that selinexor and venetoclax are synergistic and that selinexor may minimize resistance to venetoclax. The dose-escalation phase of this study will characterize the dose-limiting toxicity and determine the recommended phase 2 dose (RP2D) of venetoclax plus selinexor with and without chemotherapy. Two expansion cohorts will further assess the safety and will explore the efficacy at the RP2D. Cohort A will include patients without prior exposure to venetoclax. Cohort B will include patients with prior exposure to venetoclax.

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

Eligibility Criteria

Inclusion criteria include:

• Diagnosis of relapsed/refractory acute myeloid leukemia or acute leukemia of ambiguous lineage
• 30 years old or younger
• ≥ 5% blasts in the bone marrow
• Ineligible for curative therapy
• At least 14 days since completion of myelosuppressive therapy or hypomethylating agents and the first doses of the study drugs
• At least 24 hours since completion of low-dose or non-myelosuppressive therapy or leukapheresis and the first doses of the study drugs
• No evidence of GVHD in patients who have received prior HCT
• At least 60 days since HCT

Exclusion Criteria include:

• Pregnancy or breastfeeding
• Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia or bone marrow failure syndrome
• Impairment of gastrointestinal function or disease that may significantly alter absorption of the study drugs
• Previous toxicity or hypersensitivity to venetoclax
• History of cerebellar toxicity or cerebellar neurological findings

Study Sites

St. Jude Children’s Research Hospital
Memphis, Tennessee
Collaborating sites in the U.S.

About this study

This is a study of two new drugs called venetoclax and selinexor. Doctors want to find out if these drugs are safe and if they have beneficial effects in children, adolescents and young adults when combined with standard chemotherapy for AML. Chemotherapy is anti-cancer medicine.

The U.S. Food and Drug Administration (FDA) has approved venetoclax to treat AML and some other types of leukemia in adults. The FDA has also approved selinexor to treat certain types of lymphoma and multiple myeloma in adults. However, the FDA has not approved venetoclax or selinexor to treat AML in children.

There are two parts to this study. Part 1 will decide the highest dose of venetoclax, selinexor and chemotherapy that is safe to give patients. Part 2 will look at the effects of this treatment.

Purpose of this clinical trial

The main goals of this study are to test the safety of venetoclax and selinexor and find the highest dose that is safe to give when combined with chemotherapy drugs. Researchers also want to find out about any side effects and learn how the treatment affects your body.

Eligibility overview

• Diagnosis of one of the following:
  • Relapsed or refractory acute myeloid leukemia (AML)
  • Acute leukemia of ambiguous lineage (ALAL)
• 30 years old or younger (24 years or younger at St. Jude)
• Ineligible for other curative therapy