Back to resultsA Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
Primary Purpose
Acute Lymphoblastic Leukemia (ALL), Lymphoblastic Lymphoma
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Navitoclax
Chemotherapy
Venetoclax
Sponsored by
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia (ALL) focused on measuring Relapsed of Refractory Acute Lymphoblastic Leukemia, Cancer, Venetoclax, Navitoclax
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.
Sites / Locations
- City of Hope /ID# 169029
- LPCH Stanford /ID# 163337
- University of Chicago /ID# 163369
- Washington University-School of Medicine /ID# 165689
- Univ NC Chapel Hill /ID# 163509
- Cincinnati Children's Hospital /ID# 164619
- Nationwide Childrens Hospital /ID# 163372
- Oregon Health and Science University /ID# 165690
- St Jude Children's Research Hospital /ID# 163335
- UT Southwestern Medical Center /ID# 163346
- MD Anderson Cancer Center at Texas Medical Center /ID# 163327
- University of Wisconsin-Madiso /ID# 165691
- Alfred Hospital /ID# 169576
- Victorian Comprehensive Cancer /ID# 165710
- Royal Children's Hospital /ID# 163322
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Venetoclax + Navitoclax + Chemotherapy
Arm Description
Venetoclax weight-adjusted doses administered orally every day (QD) starting on Day 1 + navitoclax various, weight-adjusted doses administered orally QD starting on Day 3 + chemotherapy (peg-asparaginase [or any other forms of asparaginase], vincristine, dexamethasone) and tyrosine kinase inhibitor [TKI, if applicable]). This regimen and any of its components may be delayed, reduced or omitted at the discretion of the Investigator.
Outcomes
Primary Outcome Measures
Cmax of Venetoclax + Navitoclax
Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax
AUC of Venetoclax + Navitoclax
Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax
Tmax of Venetoclax + Navitoclax
Time to Cmax (Tmax) of Venetoclax + Navitoclax
CL/F of Venetoclax + Navitoclax
Apparent oral clearance (CL/F) of venetoclax + navitoclax
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.
Secondary Outcome Measures
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.
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.
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.
Overall survival (OS)
OS is defined as the number of days from the date of enrollment to the date of death.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03181126
Brief Title
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
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
November 27, 2017 (Actual)
Primary Completion Date
November 11, 2020 (Actual)
Study Completion Date
November 14, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia (ALL), Lymphoblastic Lymphoma
Keywords
Relapsed of Refractory Acute Lymphoblastic Leukemia, Cancer, Venetoclax, Navitoclax
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
69 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Venetoclax + Navitoclax + Chemotherapy
Arm Type
Experimental
Arm Description
Venetoclax weight-adjusted doses administered orally every day (QD) starting on Day 1 + navitoclax various, weight-adjusted doses administered orally QD starting on Day 3 + chemotherapy (peg-asparaginase [or any other forms of asparaginase], vincristine, dexamethasone) and tyrosine kinase inhibitor [TKI, if applicable]). This regimen and any of its components may be delayed, reduced or omitted at the discretion of the Investigator.
Intervention Type
Drug
Intervention Name(s)
Navitoclax
Other Intervention Name(s)
ABT-263
Intervention Description
tablet
Intervention Type
Drug
Intervention Name(s)
Chemotherapy
Intervention Description
peg-asparaginase (or other form of asparaginase, per local standard of care (intravenous) + vincristine (intravenous) + dexamethasone (oral) + tyrosine kinase inhibitor (TKI) (if applicable, oral)
Intervention Type
Drug
Intervention Name(s)
Venetoclax
Other Intervention Name(s)
ABT-199 GDC-0199
Intervention Description
tablet
Primary Outcome Measure Information:
Title
Cmax of Venetoclax + Navitoclax
Description
Maximum observed plasma concentration (Cmax) of venetoclax + navitoclax
Time Frame
Up to approximately 9 months
Title
AUC of Venetoclax + Navitoclax
Description
Area under the plasma concentration-time curve (AUC) of venetoclax + navitoclax
Time Frame
Up to approximately 9 months
Title
Tmax of Venetoclax + Navitoclax
Description
Time to Cmax (Tmax) of Venetoclax + Navitoclax
Time Frame
Up to approximately 9 months
Title
CL/F of Venetoclax + Navitoclax
Description
Apparent oral clearance (CL/F) of venetoclax + navitoclax
Time Frame
Up to approximately 9 months
Title
Number of participants with dose-limiting toxicities (DLT)
Description
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
Secondary Outcome Measure Information:
Title
Progression-free survival (PFS)
Description
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
Title
Partial Response (PR) rate
Description
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
Title
Number of Participant who Proceed to Stem Cell Transplantation or Chimeric antigen receptor T-cell (CAR-T) Therapy
Description
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
Title
Overall survival (OS)
Description
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
Title
Objective response rate (ORR)
Description
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
Title
Complete Response (CR) rate
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
4 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
AbbVie Inc.
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope /ID# 169029
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
LPCH Stanford /ID# 163337
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
University of Chicago /ID# 163369
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Washington University-School of Medicine /ID# 165689
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Univ NC Chapel Hill /ID# 163509
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514-4220
Country
United States
Facility Name
Cincinnati Children's Hospital /ID# 164619
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
Nationwide Childrens Hospital /ID# 163372
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Facility Name
Oregon Health and Science University /ID# 165690
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
St Jude Children's Research Hospital /ID# 163335
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
UT Southwestern Medical Center /ID# 163346
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390-7208
Country
United States
Facility Name
MD Anderson Cancer Center at Texas Medical Center /ID# 163327
City
Houston
State/Province
Texas
ZIP/Postal Code
77030-4000
Country
United States
Facility Name
University of Wisconsin-Madiso /ID# 165691
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
Facility Name
Alfred Hospital /ID# 169576
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Facility Name
Victorian Comprehensive Cancer /ID# 165710
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Facility Name
Royal Children's Hospital /ID# 163322
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3052
Country
Australia
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Links:
URL
https://www.abbvie.com/content/dam/abbvie-dotcom/us/clinical-trials/venetoclax_M16-106.pdf
Description
clinical study report synopsis
Learn more about this trial
A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
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