Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT03181126




Registration number
NCT03181126
Ethics application status
Date submitted
5/06/2017
Date registered
8/06/2017
Date last updated
14/10/2021

Titles & IDs
Public title
A Study of Venetoclax in Combination With Navitoclax and Chemotherapy in Subjects With Relapsed/Refractory Acute Lymphoblastic Leukemia or Relapsed/Refractory Lymphoblastic Lymphoma
Scientific 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
Secondary ID [1] 0 0
M16-106
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Lymphoblastic Leukemia (ALL) 0 0
Lymphoblastic Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Navitoclax
Treatment: Drugs - Chemotherapy
Treatment: Drugs - Venetoclax

Experimental: Venetoclax + Navitoclax + Chemotherapy - 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.


Treatment: Drugs: Navitoclax
tablet

Treatment: Drugs: Chemotherapy
peg-asparaginase (or other form of asparaginase, per local standard of care (intravenous) + vincristine (intravenous) + dexamethasone (oral) + tyrosine kinase inhibitor (TKI) (if applicable, oral)

Treatment: Drugs: Venetoclax
tablet
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Cmax of Venetoclax + Navitoclax
Timepoint [1] 0 0
Up to approximately 9 months
Primary outcome [2] 0 0
AUC of Venetoclax + Navitoclax
Timepoint [2] 0 0
Up to approximately 9 months
Primary outcome [3] 0 0
Tmax of Venetoclax + Navitoclax
Timepoint [3] 0 0
Up to approximately 9 months
Primary outcome [4] 0 0
CL/F of Venetoclax + Navitoclax
Timepoint [4] 0 0
Up to approximately 9 months
Primary outcome [5] 0 0
Number of participants with dose-limiting toxicities (DLT)
Timepoint [5] 0 0
Up to approximately 28 days after initial dose of study drug
Secondary outcome [1] 0 0
Progression-free survival (PFS)
Timepoint [1] 0 0
Up to 9 months after the last subject has enrolled into the study
Secondary outcome [2] 0 0
Partial Response (PR) rate
Timepoint [2] 0 0
Up to 9 months after the last subject has enrolled into the study
Secondary outcome [3] 0 0
Number of Participant who Proceed to Stem Cell Transplantation or Chimeric antigen receptor T-cell (CAR-T) Therapy
Timepoint [3] 0 0
Up to 9 months after the last subject has enrolled into the study
Secondary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
Up to 9 months after the last subject has enrolled into the study
Secondary outcome [5] 0 0
Objective response rate (ORR)
Timepoint [5] 0 0
Up to 9 months after the last subject has enrolled into the study
Secondary outcome [6] 0 0
Complete Response (CR) rate
Timepoint [6] 0 0
Up to 9 months after the last subject has enrolled into the study

Eligibility
Key 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.
Minimum age
4 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/11/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
14/11/2020
Sample size
Target
Accrual to date
Final
69
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Alfred Hospital /ID# 169576 - Melbourne
Recruitment hospital [2] 0 0
Victorian Comprehensive Cancer /ID# 165710 - Melbourne
Recruitment hospital [3] 0 0
Royal Children's Hospital /ID# 163322 - Melbourne
Recruitment postcode(s) [1] 0 0
3004 - Melbourne
Recruitment postcode(s) [2] 0 0
3050 - Melbourne
Recruitment postcode(s) [3] 0 0
3052 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Oregon
Country [7] 0 0
United States of America
State/province [7] 0 0
Tennessee
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Wisconsin

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT03181126
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AbbVie Inc.
Address 0 0
AbbVie
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT03181126