This dose-escalating study is to determine the safety, pharmacokinetics, and preliminary efficacy of venetoclax in combination with navitoclax and chemotherapy in adult and pediatric participants with relapsed/refractory acute lymphoblastic leukemia (ALL) or relapsed/refractory lymphoblastic lymphoma. A safety expansion cohort of approximately 20 patients may be enrolled in addition to the 50 participants in dose-escalation cohort.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
69
tablet
peg-asparaginase (or other form of asparaginase, per local standard of care (intravenous) + vincristine (intravenous) + dexamethasone (oral) + tyrosine kinase inhibitor (TKI) (if applicable, oral)
tablet
City of Hope /ID# 169029
Duarte, California, United States
LPCH Stanford /ID# 163337
Palo Alto, California, United States
University of Chicago /ID# 163369
Chicago, Illinois, United States
Washington University-School of Medicine /ID# 165689
St Louis, Missouri, United States
Univ NC Chapel Hill /ID# 163509
Chapel Hill, North Carolina, United States
Cincinnati Children's Hospital /ID# 164619
Cincinnati, Ohio, United States
Nationwide Childrens Hospital /ID# 163372
Columbus, Ohio, United States
Oregon Health and Science University /ID# 165690
Portland, Oregon, United States
St Jude Children's Research Hospital /ID# 163335
Memphis, Tennessee, United States
UT Southwestern Medical Center /ID# 163346
Dallas, Texas, United States
...and 5 more locations
Cmax of Venetoclax + Navitoclax
Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax
Time frame: Up to approximately 9 months
AUC of Venetoclax + Navitoclax
Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax
Time frame: Up to approximately 9 months
Tmax of Venetoclax + Navitoclax
Time to Cmax (Tmax) of Venetoclax + Navitoclax
Time frame: Up to approximately 9 months
CL/F of Venetoclax + Navitoclax
Apparent oral clearance (CL/F) of venetoclax + navitoclax
Time frame: Up to approximately 9 months
Number of participants with dose-limiting toxicities (DLT)
A DLT is any Grade 3 or higher non-hematologic adverse event (AE) with exceptions outlined in the protocol. AEs and toxicities that occur beyond the DLT assessment period will also be evaluated by the investigator and AbbVie and may be considered as dose-limiting.
Time frame: Up to approximately 28 days after initial dose of study drug
Progression-free survival (PFS)
PFS is defined as the number of days from the date of enrollment to the date of earliest disease progression or death.
Time frame: Up to 9 months after the last subject has enrolled into the study
Partial Response (PR) rate
PR defined as no peripheral blasts or peripheral blood absolute blast count decreased by ≥ 50% from baseline, bone marrow with 5 - 25% blasts and at least a 50% decrease in bone marrow blast percent from baseline, no evidence of extramedullary disease.
Time frame: Up to 9 months after the last subject has enrolled into the study
Number of Participant who Proceed to Stem Cell Transplantation or Chimeric antigen receptor T-cell (CAR-T) Therapy
Determine the number of participants who proceed to stem cell transplantation or CAR-T therapy.
Time frame: Up to 9 months after the last subject has enrolled into the study
Overall survival (OS)
OS is defined as the number of days from the date of enrollment to the date of death.
Time frame: Up to 9 months after the last subject has enrolled into the study
Objective response rate (ORR)
The proportion of subjects with objective response rate (complete response \[CR\] + CR incomplete recovery \[CRi\] + CR without platelet recovery \[CRp\]) for ALL subjects and (CR+PR) for LL subjects.
Time frame: Up to 9 months after the last subject has enrolled into the study
Complete Response (CR) rate
CR defined as hematologic recovery (absolute neutrophil count \[ANC\] greater than or equal to 500/μL; platelet counts greater than or equal to 75,000/μL), evidence of trilineage hematopoiesis in the bone marrow and less than 5% blasts in the bone marrow, absence of circulating blasts, and no evidence of extramedullary disease.
Time frame: Up to 9 months after the last subject has enrolled into the study
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