VENAML: Chemotherapy Combined with Venetoclax in Children with Refractory or Relapsed Acute Myeloid Leukemia

A Phase I and Expansion Cohort Study of Venetoclax in Combination with Chemotherapy in Pediatric Patients with Refractory or Relapsed Acute Myeloid Leukemia

Categories:

Leukemia / Lymphoma

Phase I/II

Diseases Treated:

Acute myeloid leukemia (AML)

Eligibility Overview:

  • Diagnosis of relapsed or refractory acute myeloid leukemia (AML)
  • Between 2 and 21 years old
  • Able to swallow pills
  • Recovered from acute effects of prior therapy and no evidence of graft-versus-host disease (GVHD)
  • Adequate liver, kidney and heart functions
  1. Brief Summary

    Current survival rates for children with refractory or relapsed AML are poor, with fewer than 40% of these patients becoming long-term survivors. Most treatments for patients with relapsed AML are based on conventional chemotherapeutic agents, such as cytarabine, followed by hematopoietic stem cell transplantation. This clinical trial will study the safety and activity of venetoclax, a BCL-2 inhibitor, in combination with chemotherapy for pediatric patients with relapsed or refractory AML.  Preclinical and emerging clinical data have shown venetoclax to be active and tolerable in adult patients with AML. The early responses seen in adult patients treated with venetoclax and very low-dose cytarabine suggest treatment with venetoclax may sensitize AML cells to cytarabine.

    The FDA has approved venetoclax to treat chronic lymphocytic leukemia (CLL) in patients with a 17p deletion chromosomal abnormality who have failed prior therapy.

    Primary Objective

    • To determine a tolerable combination of venetoclax plus chemotherapy in pediatric patients with relapsed or refractory AML

    Secondary Objective

    • To estimate the overall response rate to the combination of venetoclax and chemotherapy in pediatric patients with relapsed or refractory AML.

    Eligibility Criteria

    Inclusion criteria, among others:

    • Diagnosis of relapsed or refractory acute myeloid leukemia (AML)
    • Between 2 and 21 years old
    • Able to swallow pills
    • Recovered from acute effects of prior therapy and no evidence of graft-versus-host disease (GVHD)
    • Adequate liver, kidney and heart functions

    Exclusion Criteria include:

    • Pregnancy or breastfeeding
    • Down syndrome, acute promyelocytic leukemia, juvenile myelomonocytic leukemia, or bone marrow failure syndrome
    • Gastrointestinal impairment

    Study Sites

    St. Jude Children’s Research Hospital
    Memphis, Tennessee

    Collaborating sites in the U.S.

  2. About this study

    This study will test a new drug, called venetoclax, in children with acute myeloid leukemia (AML) that did not respond to prior therapy (refractory) or that came back after previous treatment (relapsed). Venetoclax is also known as also called Venclexta®. It is a type of drug called a BCL-2 inhibitor. The drug binds to a protein called BCL-2, which may be found on some types of leukemia cells. Blocking this protein may help kill cancer cells and make them more sensitive to other anti-cancer chemotherapy drugs.

    The FDA has approved venetoclax to treat another kind of leukemia, called chronic lymphocytic leukemia (CLL), in adults who have received other treatments. It is used in patients whose cancer has a change in chromosome 17. The FDA has not approved venetoclax to treat childhood AML.

    Purpose of this clinical trial

    The main purpose of this study is to find out the best dose of venetoclax and chemotherapy that can be given safely to children with AML. Researchers also want to find out how AML responds to this combination treatment.

    Eligibility overview

    • Diagnosis of relapsed or refractory acute myeloid leukemia (AML):
    • Between 2 and 21 years old
    • Able to swallow pills
    • Recovered from acute effects of prior therapy and no evidence of graft-versus-host disease (GVHD)
    • Adequate liver, kidney and heart functions
  3. VENAML Quick View
    Sponsors St. Jude Children's Research Hospital
    ClinicalTrials.gov identifier NCT03194932
    Trial Start Date July 2017
    Estimated Enrollment 54
    Study Type Interventional
    Study Phase Phase I
    Conditions Acute myeloid leukemia (AML)
    Ages 2 to 21 years old
    Principal investigator Jeffrey Rubnitz, MD, PhD
    Study Sites St. Jude Children's Research Hospital and collaborating sites in the U.S.
    For a consultation or to discuss VENAML St. Jude Physician/Patient Referral Office
    1-888-226-4343
    referralinfo@stjude.org

Contact

St. Jude Children’s Research Hospital
262 Danny Thomas Place
Memphis, TN 38105  USA
Voice: 1-888-226-4343 or 901-595-4055
24-Hour Emergency Access Pager: 1-800-349-4334
Email: referralinfo@stjude.org

The above information is intended to provide only a basic description about a research protocol that may be currently active at St. Jude. The details made available here may not be the most up-to-date information on protocols used by St. Jude. To receive full details about a protocol and its status and or use at St. Jude, a physician must contact St. Jude directly.