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.
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
Interventions
| Drug | Synonyms | Arms |
|---|
| Vyxeos | cytarabine and daunorubicin liposome, CPX-351 | Venetoclax and Vyxeos combination |
| Venetoclax | Venclexta | Venetoclax 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
| Name | Type | Description | Interventions |
|---|
| Venetoclax and Vyxeos combination | Experimental | 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. | |
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
| 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)
Last Updated
November 9, 2020
