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

Sponsor

Children's Hospital Medical Center, Cincinnati (Other)

Overall Status

Suspended

CT.gov ID

NCT03826992

Collaborator

(none)

Enrollment

Location

Arm

60.2

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

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.

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

N/A

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 :

Dec 27, 2018

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Jan 1, 2024

Arms and Interventions

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 Names: cytarabine and daunorubicin liposome, CPX-351 Drug: Venetoclax Venetoclax Dose: Dose Level 0 - 400 mg daily for 21 days Dose Level -1 - 400 mg daily for 14 days Other Names: Venclexta

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 Names:

cytarabine and daunorubicin liposome, CPX-351

Drug: Venetoclax

Venetoclax Dose: Dose Level 0 - 400 mg daily for 21 days Dose Level -1 - 400 mg daily for 14 days

Other Names:

Venclexta

Outcome Measures

Primary Outcome Measures

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.
Treatment related toxicities [60 days]
Number of related adverse events

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year to 39 Years

Sexes Eligible for Study:

All

Accepts 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