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

Leukemia Clinical Trial

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 Details — Status: Recruiting

Administrative data

• NCT number: NCT03826992
• Other study ID #: V2-MA-1801
• Status: Recruiting
• Phase: Phase 1
• Start date: December 27, 2018
• Est. completion date: January 2026

Study information

• Verified date: January 2024
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Site Pulblic Contact
• Phone: 513-636-2799
• Email: cancer[@]cchmc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: January 2026
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 39 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia

Intervention

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.
• Venetoclax
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

Locations

Country	Name	City	State
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	28 days
Primary	Treatment related toxicities	Number of related adverse events	60 days
Secondary	Disease response	Estimate of overall response rate (ORR) defined as (CR/CRi/CRp).	42 days
Secondary	Cancer therapeutics-related cardiac dysfunction (CTRCD) in patients who have previously received anthracyclines	Measured by echocardiogram (ECHO)	60 days

External Links

•   Cincinnati Children's Cancer and Blood Diseases Institute
•   Cincinnati Children's Hospital Oncology Division
•   Leukemia and Lymphoma Program