Clinical Trials /

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

NCT03826992

Description:

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.

Related Conditions:
  • Acute Lymphoblastic Leukemia
  • Acute Myeloid Leukemia
  • Acute Undifferentiated Leukemia
  • Mixed Phenotype Acute Leukemia
  • T-Cell Acute Lymphoblastic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Venetoclax Combined With Vyxeos (CPX-351) for Participants With Relapsed or Refractory Acute Leukemia
  • Official Title: A Phase I Study of Venetoclax Combined With Vyxeos (CPX-351) for Children, Adolescents and Young Adults With Relapsed or Refractory Acute Leukemia

Clinical Trial IDs

  • ORG STUDY ID: V2-MA-1801
  • NCT ID: NCT03826992

Conditions

  • Leukemia

Interventions

DrugSynonymsArms
Vyxeoscytarabine and daunorubicin liposome, CPX-351Venetoclax and Vyxeos combination
VenetoclaxVenclextaVenetoclax and Vyxeos combination

Purpose

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 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.
    

Trial Arms

NameTypeDescriptionInterventions
Venetoclax and Vyxeos combinationExperimentalVenetoclax will be given orally on Days 1-21 per the assigned dose level. A single course consisting of 3 doses of Vyxeos and 21 doses of venetoclax 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.
  • Vyxeos
  • Venetoclax

Eligibility Criteria

        Inclusion Criteria:

          -  Ages 1-39 years

          -  Diagnosis of one of the following:

               -  Acute myeloid leukemia (AML)

               -  Acute undifferentiated leukemia (AUL)

               -  Mixed phenotype acute leukemia (MPAL)

               -  T-cell acute lymphoblastic leukemia (T ALL)

               -  Early thymocyte precursor (ETP) ALL

               -  KMT2A-rearranged ALL

          -  Disease status

               -  Relapsed/Refractory AML, MPAL and AUL

               -  Untreated therapy related AML

               -  Relapsed/Refractory KMT2A-rearranged ALL, T-cell ALL, ETP 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:

               -  Acute Promyelocytic Leukemia (APML)

               -  Acute leukemia with CNS status 3 involvement

               -  Philadelphia chromosome positive leukemia (Ph+ ALL, 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

          -  Unable to swallow tablets

          -  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
      
Maximum Eligible Age:39 Years
Minimum Eligible Age:1 Year
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Feasibility of combining venetoclax and Vyxeos (dose limiting toxicities)
Time Frame:28 days
Safety Issue:
Description: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

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Children's Hospital Medical Center, Cincinnati

Trial Keywords

  • relapsed
  • refractory
  • Vyxeos
  • Venetoclax
  • acute myeloid leukemia
  • acute myeloid leukemia, childhood
  • mixed-lineage leukemia (MLL)
  • AML
  • CPX-351
  • Venclexta
  • Histone-lysine N-methyltransferase 2A (KmT2A)

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