Venetoclax Combined With Vyxeos (CPX-351) for Participants With Relapsed or Refractory Acute Leukemia

Phase 1

Recruiting

• Conditions: Leukemia
• Interventions: Drug: Vyxeos; Drug: Venetoclax

• Registration Number: NCT03826992
• Lead Sponsor: Children's Hospital Medical Center, Cincinnati

Brief Summary

This study evaluates the safety and tolerability of combining venetoclax with Vyxeos (CPX-351) in pediatric and young adult patients with acute leukemia that has come back or not responded to treatment.

Detailed Description

This is a single-institution Phase I pilot study designed to test the safety and tolerability of combining venetoclax with Vyxeos (CPX-351, cytarabine and daunorubicin liposome) for the treatment of relapsed/refractory acute leukemia in young patients. Subjects will receive a single course of study therapy consisting of daily, oral or crushed venetoclax at an assigned dose level with a 3-day ramp-up to target dose and Vyxeos administered intravenously at the established dose on Days 1, 3, and 5. In addition to safety and tolerability, the overall response rate to these therapies will be estimated. Pharmacokinetic (PK) analysis will also be conducted to define the drug clearance of venetoclax in this combination.

Study Timeline

• Study Start: 2018-12-27
• Study First Submitted: 2019-01-09
• Study First Submitted QC: 2019-01-31
• Study First Posted: 2019-02-01
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-14
• Primary Completion: 2027-01
• Study Completion: 2028-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Ages 1 Year to 39 Years

• Diagnosis of one of the following:

  • Acute myeloid leukemia (AML), any subtype except

    • Patients with acute promyelocytic leukemia (APML) are NOT eligible
    • Patients with ML-DS are NOT eligible

  • Myeloid sarcoma

  • Acute leukemia of ambiguous lineage (ALAL)

    • Acute undifferentiated leukemia (AUL)
    • T/myeloid mixed phenotype acute leukemia (MPAL)
    • B/myeloid MPAL
    • MPAL with KMT2A-rearrangement MPAL with t (9;22) are NOT eligible

  • T-cell acute lymphoblastic leukemia (T ALL)

  • Early thymocyte precursor (ETP) ALL

  • KMT2A-rearranged ALL

• Disease Status

  • Relapsed/Refractory AML, MPA, and AUL
  • Untreated therapy related AML
  • Relapsed/Refractory KMT2A-rearranged ALL, T-cell ALL, ETEP ALL

• Karnofsky/Lanksy performance level score of greater than or equal to 50 percent.

• Prior therapy requirements

  • Fully recovered from acute toxicities of Hematopoietic Stem Cell Transplant (HSCT) or Anthracycline Exposure
  • 14 days must have elapsed since the completion of systemic cytotoxic therapy other than hydroxyurea, decitabine or azacitidine
  • 2 weeks must have elapsed for local palliative radiotherapy (RT); 6 months must have elapsed if prior craniospinal RT or if 50% radiation of pelvis, and at least 6 weeks must have elapsed if other substantial bone marrow radiation

• Adequate renal, liver, cardiac, and central nervous system (CNS) function

Exclusion Criteria

• Diagnosis of one of the following:

  • Myeloid Leukemia associated with Down Syndrome (ML-DS)
  • Acute Promyelocytic Leukemia (APML)
  • Acute leukemia with CNS status 3 involvement
  • Philadelphia chromosome t(9;22) positive leukemia (Ph+ ALL, AML, MPAL, or AUL)
  • Fanconi Anemia, Shwachman-Diamond syndrome, or any other bone marrow failure syndrome or DNA repair disorder
  • Wilson's Disease or other copper-metabolism disorder

• Pregnant or breastfeeding

• Uncontrolled infection

• Received greater than 13.6 Gray (Gy) prior radiation to the mediastinum

• Receipt of growth factors within 7 days prior to enrollment

• Currently receiving another investigational drug

• Currently receiving anti-cancer agents (with the exception of intrathecal (IT) agents or hydroxyurea)

• Unable to comply with the safety monitoring requirements of the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Venetoclax and Vyxeos combination	Vyxeos	Venetoclax will be given orally on Days per the assigned dose level. A single course consisting of 3 doses of Vyxeos and 7-21 doses of venetoclax depending on the assigned dose level will be administered to participants in this study. Vyxeos will be administered by central venous catheter over 90 minutes on Day 1, 3, and 5. Venetoclax is given daily by mouth per assigned dose level.
Venetoclax and Vyxeos combination	Venetoclax	Venetoclax will be given orally on Days per the assigned dose level. A single course consisting of 3 doses of Vyxeos and 7-21 doses of venetoclax depending on the assigned dose level will be administered to participants in this study. Vyxeos will be administered by central venous catheter over 90 minutes on Day 1, 3, and 5. Venetoclax is given daily by mouth per assigned dose level.

Primary Outcome Measures

Name	Time	Method
Treatment related toxicities	60 days	Number of related adverse events
Feasibility of combining venetoclax and Vyxeos (dose limiting toxicities)	28 days	If 2 or more participants have dose limiting toxicities at a given dose level, the maximum tolerated dose will have been exceeded.

Secondary Outcome Measures

Name	Time	Method
Cancer therapeutics-related cardiac dysfunction (CTRCD) in patients who have previously received anthracyclines	60 days	Measured by echocardiogram (ECHO)
Disease response	42 days	Estimate of overall response rate (ORR) defined as (CR/CRi/CRp).

Trial Locations

Locations (1)

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States