Clinical trial NCT03181126: A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
Official title: A Phase 1 Dose Escalation, Open-Label Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Lymphoblastic Leukemia (ALL)
Lymphoblastic Lymphoma
Keywords: Relapsed of Refractory Acute Lymphoblastic Leukemia
Cancer
Venetoclax
Navitoclax
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-06-08
Enrollment: 69
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Must have relapsed or refractory acute lymphoblastic leukemia (ALL) or relapsed or refractory lymphoblastic lymphoma (LL). Refractory is defined as persistent disease after at least 2 courses of chemotherapy.

  * Participants with ALL with Philadelphia chromosome or with an ABL class targetable fusion are eligible.
  * Participants with LL must have radiographic evidence of disease
* Participants \<= 18 years of age who do not have a standard of care treatment option available.
* Must weigh greater than or equal to 20 kg.
* Must be able to swallow pills.
* Must have adequate hepatic and kidney function.
* Must have adequate performance status:

  * Participants less than or equal to 16 years of age: Lansky greater than or equal to 50
  * Participants greater than 16 years of age: Karnofsky greater than or equal to 50 or Eastern Cooperative Oncology Group (ECOG) less than 3.

Exclusion Criteria:

* Participant has central nervous system (CNS) disease with cranial involvement that requires radiation.
* Participants who are less than 100 days post-transplant, or greater than 100 days post-transplant with active graft versus host disease (GVHD), or are still continuing post-transplant immunosuppressant therapy within 7 days prior to the first dose of study drug.
* Participants who have received any of the following prior to the first dose of study drug:

  * Inotuzumab within 30 days (if participant received inotuzumab \> 30 days prior to Day 1, must have ALT, AST and bilirubin \< ULN).
  * A biologic agent (i.e., monoclonal antibodies) for anti-neoplastic intent within 30 days
  * CAR-T infusion or other cellular therapy within 30 days
  * Any anti-cancer therapy including blinatumomab, chemotherapy, radiation therapy targeted small molecule agents or investigational agents within 14 days, or 5 half-lives, whichever is shorter

    * Exception: Philadelphia Chromosome (Ph)+ ALL subjects on TKIs at Screening may enroll and remain on Tyrosine Kinase Inhibitor (TKI) therapy to control disease. Participants on venetoclax at screening may enroll and remain on venetoclax.
  * Steroid therapy for anti-neoplastic intent within 5 days
  * Hydroxyurea that is ongoing (hydroxyurea is permitted up to the first dose)
  * A strong or moderate CYP3A inhibitor or inducer within 7 days
  * Aspirin within 7 days, or 5 half-lives, whichever is longer
  * An excluded antiplatelet/anticoagulant drug or a herbal supplement that affects platelet function within 7 days, or 5 half-lives, whichever is longer
* Participants with malabsorption syndrome or any other condition that precludes enteral administration.

Primary outcomes:
measure: Cmax of Venetoclax + Navitoclax
timeFrame: Up to approximately 9 months
measure: AUC of Venetoclax + Navitoclax
timeFrame: Up to approximately 9 months
measure: Tmax of Venetoclax + Navitoclax
timeFrame: Up to approximately 9 months
measure: CL/F of Venetoclax + Navitoclax
timeFrame: Up to approximately 9 months
measure: Number of participants with dose-limiting toxicities (DLT)
timeFrame: Up to approximately 28 days after initial dose of study drug
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 9 months after the last subject has enrolled into the study
measure: Partial Response (PR) rate
timeFrame: Up to 9 months after the last subject has enrolled into the study
measure: Number of Participant who Proceed to Stem Cell Transplantation or Chimeric antigen receptor T-cell (CAR-T) Therapy
timeFrame: Up to 9 months after the last subject has enrolled into the study
measure: Overall survival (OS)
timeFrame: Up to 9 months after the last subject has enrolled into the study
measure: Objective response rate (ORR)
timeFrame: Up to 9 months after the last subject has enrolled into the study
measure: Complete Response (CR) rate
timeFrame: Up to 9 months after the last subject has enrolled into the study
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope /ID# 169029
state: California
city: Palo Alto
country: United States
facility: LPCH Stanford /ID# 163337
state: California
city: Chicago
country: United States
facility: University of Chicago /ID# 163369
state: Illinois
city: Saint Louis
country: United States
facility: Washington University-School of Medicine /ID# 165689
state: Missouri
city: Chapel Hill
country: United States
facility: Univ NC Chapel Hill /ID# 163509
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital /ID# 164619
state: Ohio
city: Columbus
country: United States
facility: Nationwide Childrens Hospital /ID# 163372
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University /ID# 165690
state: Oregon
city: Memphis
country: United States
facility: St Jude Children's Research Hospital /ID# 163335
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center /ID# 163346
state: Texas
city: Houston
country: United States
facility: MD Anderson Cancer Center at Texas Medical Center /ID# 163327
state: Texas
city: Madison
country: United States
facility: University of Wisconsin-Madiso /ID# 165691
state: Wisconsin
city: Melbourne
country: Australia
facility: Alfred Hospital /ID# 169576
state: Victoria
city: Melbourne
country: Australia
facility: Victorian Comprehensive Cancer /ID# 165710
state: Victoria
city: Melbourne
country: Australia
facility: Royal Children's Hospital /ID# 163322
state: Victoria
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References: