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

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ClinicalTrials.gov Identifier: NCT03826992
Recruitment Status : Recruiting
First Posted : February 1, 2019
Last Update Posted : October 8, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Leukemia Drug: Vyxeos Drug: Venetoclax Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : December 27, 2018
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2023


Arm Intervention/treatment
Experimental: Venetoclax and Vyxeos combination

Venetoclax 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.

Drug: Vyxeos
Vyxeos Dose: daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 administered via intravenous infusion over 90 minutes on days 1, 3, and 5.
Other Name: cytarabine and daunorubicin liposome, CPX-351

Drug: Venetoclax

Venetoclax Dose:

  1. Dose Level 0- allometrically scaled to 400 mg
  2. Dose Level 1- allometrically scaled to 600 mg
  3. Dose Level -1- allometrically scaled to 250 mg
Other Name: Venclexta




Primary Outcome Measures :
  1. Feasibility of combining venetoclax and Vyxeos (dose limiting toxicities) [ Time Frame: 28 days ]
    If 2 or more participants have dose limiting toxicities at a given dose level, the maximum tolerated dose will have been exceeded.

  2. Treatment related toxicities [ Time Frame: 60 days ]
    Number of related adverse events


Secondary Outcome Measures :
  1. Disease response [ Time Frame: 42 days ]
    Estimate of overall response rate (ORR) defined as (CR/CRi/CRp).

  2. Cancer therapeutics-related cardiac dysfunction (CTRCD) in patients who have previously received anthracyclines [ Time Frame: 60 days ]
    Measured by echocardiogram (ECHO)



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Year to 39 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03826992


Contacts
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Contact: Site Pulblic Contact 513-636-2799 cancer@cchmc.org

Locations
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United States, Ohio
Cincinnati Children's Hospital Medical Center Recruiting
Cincinnati, Ohio, United States, 45229
Contact: Site Public Contact    513-636-2799    cancer@cchmc.org   
Principal Investigator: Michael Absalon, MD, PhD         
Principal Investigator: Laura Agresta, MD         
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
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Principal Investigator: Michael Absalon, MD, PhD Children's Hospital Medical Center, Cincinnati
Principal Investigator: Laura Agresta, MD Children's Hospital Medical Center, Cincinnati

Additional Information:
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Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT03826992     History of Changes
Other Study ID Numbers: V2-MA-1801
First Posted: February 1, 2019    Key Record Dates
Last Update Posted: October 8, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Children's Hospital Medical Center, Cincinnati:
Venetoclax
Venclexta
relapsed
refractory
Vyxeos
acute myeloid leukemia
acute myeloid leukemia, childhood
mixed-lineage leukemia (MLL)
AML
CPX-351
Histone-lysine N-methyltransferase 2A (KmT2A)
Additional relevant MeSH terms:
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Venetoclax
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors