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

Primary Purpose

Leukemia

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Vyxeos
Venetoclax
Sponsored by
Children's Hospital Medical Center, Cincinnati
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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)

Eligibility Criteria

1 Year - 39 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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
    • 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

Sites / Locations

  • Cincinnati Children's Hospital Medical CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Venetoclax and Vyxeos combination

Arm Description

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
January 9, 2019
Last Updated
April 18, 2023
Sponsor
Children's Hospital Medical Center, Cincinnati
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1. Study Identification

Unique Protocol Identification Number
NCT03826992
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 27, 2018 (Actual)
Primary Completion Date
January 2025 (Anticipated)
Study Completion Date
January 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Children's Hospital Medical Center, Cincinnati

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia
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)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Venetoclax and Vyxeos combination
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Vyxeos
Other Intervention Name(s)
cytarabine and daunorubicin liposome, CPX-351
Intervention Description
Vyxeos Dose: daunorubicin 44 mg/m2 and cytarabine 100 mg/m2 administered via intravenous infusion over 90 minutes on Days 1, 3, and 5.
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
Venclexta
Intervention Description
Venetoclax Dose: Dose Level 0 - weight based daily dosing for 21 days Dose Level -1 - weight based daily dosing for 14 days Dose Level -2- weight based daily dosing for 10 days Dose Level -3- weight based daily dosing for 7 days
Primary Outcome Measure Information:
Title
Feasibility of combining venetoclax and Vyxeos (dose limiting toxicities)
Description
If 2 or more participants have dose limiting toxicities at a given dose level, the maximum tolerated dose will have been exceeded.
Time Frame
28 days
Title
Treatment related toxicities
Description
Number of related adverse events
Time Frame
60 days
Secondary Outcome Measure Information:
Title
Disease response
Description
Estimate of overall response rate (ORR) defined as (CR/CRi/CRp).
Time Frame
42 days
Title
Cancer therapeutics-related cardiac dysfunction (CTRCD) in patients who have previously received anthracyclines
Description
Measured by echocardiogram (ECHO)
Time Frame
60 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Site Pulblic Contact
Phone
513-636-2799
Email
cancer@cchmc.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John Perentesis, MD
Organizational Affiliation
Children's Hospital Medical Center, Cincinnati
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cincinnati Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Site Public Contact
Phone
513-636-2799
Email
cancer@cchmc.org
First Name & Middle Initial & Last Name & Degree
John Perentesis, MD
First Name & Middle Initial & Last Name & Degree
Laura Agresta, MD

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
http://www.cincinnatichildrens.org/research/divisions/c/cbdi/default/
Description
Cincinnati Children's Cancer and Blood Diseases Institute
URL
http://www.cincinnatichildrens.org/research/divisions/o/oncology/default/
Description
Cincinnati Children's Hospital Oncology Division
URL
http://www.cincinnatichildrens.org/service/l/leukemia-lymphoma/clinical-trials/
Description
Leukemia and Lymphoma Program

Learn more about this trial

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

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