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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03797261




Registration number
NCT03797261
Ethics application status
Date submitted
7/01/2019
Date registered
9/01/2019
Date last updated
17/05/2019

Titles & IDs
Public title
A Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies
Scientific title
Phase 1b Study of Venetoclax and AMG 176 in Patients With Relapsed/Refractory Hematologic Malignancies
Secondary ID [1] 0 0
M16-785
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Non-Hodgkin's Lymphoma 0 0
Diffuse Large B-cell 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
Description of intervention(s) / exposure
Treatment: Drugs - Venetoclax
Treatment: Drugs - AMG 176

Experimental: Venetoclax + AMG 176 - Venetoclax and AMG 176 will be administered in combination. Different combinations of dose levels for venetoclax and AMG 176 will be explored.


Treatment: Drugs: Venetoclax
tablet, oral

Treatment: Drugs: AMG 176
solution, intravenous

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

Outcomes
Primary outcome [1] 0 0
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176 - The MTD and/or RPTD of venetoclax and of AMG 176 will be determined during the dose escalation phase of the study.
Timepoint [1] 0 0
Up to 28 days after first dose of study drug in a dose-escalation phase
Primary outcome [2] 0 0
Number of Participants With Adverse Events - An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.
Timepoint [2] 0 0
From first dose of study drug until 30 days or 5 half-lives after discontinuation of study drug administration will be collected (up to approximately 4 years).
Secondary outcome [1] 0 0
Composite Complete Remission Rate (CRc) for Participants with AML - CRc rate is defined as CR + CRi (CR with incomplete blood count recovery).
Timepoint [1] 0 0
Up to approximately 2 years from last subject first dose
Secondary outcome [2] 0 0
Objective Response Rate (ORR) for Participants with AML - ORR is defined as the percentage of participants with documented partial response (PR) or better (CR + CRi + partial response [PR]) based on International Working Group (IWG) criteria for AML
Timepoint [2] 0 0
Up to approximately 2 years from last subject first dose
Secondary outcome [3] 0 0
ORR for Participants with NHL - ORR is defined as the percentage of participants with documented CR + PR based on Lugano criteria for NHL.
Timepoint [3] 0 0
Up to approximately 2 years from last subject first dose
Secondary outcome [4] 0 0
Maximum Plasma Concentration (Cmax) of Venetoclax - Maximum observed plasma concentration (Cmax) of venetoclax.
Timepoint [4] 0 0
Up to approximately 28 days after first dose of study drug
Secondary outcome [5] 0 0
Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax - Time to maximum plasma concentration (Tmax) of Venetoclax.
Timepoint [5] 0 0
Up to approximately 28 days after first dose of study drug
Secondary outcome [6] 0 0
AUC of Venetoclax - Area under the plasma concentration-time curve (AUC) of venetoclax.
Timepoint [6] 0 0
Up to approximately 28 days after first dose of study drug
Secondary outcome [7] 0 0
Maximum Plasma Concentration (Cmax) of AMG 176 - Maximum observed plasma concentration (Cmax) of AMG 176
Timepoint [7] 0 0
Up to approximately 16 days after first dose of study drug
Secondary outcome [8] 0 0
Half-life (t1/2) of AMG 176 - Terminal phase elimination half-life (t1/2)
Timepoint [8] 0 0
Approximately 16 days after first dose of study drug
Secondary outcome [9] 0 0
AUC of AMG 176 - Area Under the Plasma Concentration-time Curve (AUC) of AMG 176
Timepoint [9] 0 0
Approximately 16 days after first dose of study drug
Secondary outcome [10] 0 0
Clearance (CL) of AMG 176 - Clearance (CL) is defined the volume of plasma cleared of the drug per unit time.
Timepoint [10] 0 0
Approximately 16 days after first dose of study drug

Eligibility
Key inclusion criteria
- Adequate kidney, liver and hematology values as described in the protocol.

- Diagnosis of relapsed or refractory (R/R) acute myeloid leukemia (AML) or R/R
Non-Hodgkin's lymphoma (NHL)/diffuse large B-cell lymphoma (DLBCL) confirmed by the
World Health Organization (WHO) criteria, as appropriate.

- Meets the following disease activity criteria:

- AML: must have received at least 1 prior therapy for AML and be ineligible for
cytotoxic therapy and allogeneic stem cell transplant.

- NHL/DLBCL: measurable disease with a bidimensional lesion measuring at least 1.5 cm;
received at least 1 prior therapy for NHL with no curative treatment option as
determined by the investigator and be ineligible for a stem cell transplant.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- History of clinically significant medical condition that, in the opinion of the
investigator, would adversely affect participation in this study.

- History of of any malignancy within the last 6 months except for those specified in
this protocol and low-grade malignancies not requiring active treatment such as
non-melanoma skin cancer, cervical intraepithelial neoplasia, or prostate cancer in
situ.

- Prior allogeneic stem cell transplant or autologous stem cell transplant within 100
days of study drug administration and no signs or symptoms of acute or chronic
graft-versus-host disease.

- Previous enrollment in a randomized trial including either venetoclax or AMG 176.

- Known active or chronic pancreatitis; severe chronic obstructive pulmonary disease
with hypoxemia; central nervous system manifestations of malignancy.

- Active, uncontrolled infection.

Study design
Purpose of the study
Treatment
Allocation to intervention
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
Other
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC
Recruitment hospital [1] 0 0
Calvary Mater Newcastle /ID# 211455 - Waratah
Recruitment hospital [2] 0 0
Royal Adelaide Hospital /ID# 210602 - Adelaide
Recruitment hospital [3] 0 0
St. Vincents Hosp Melbourne /ID# 210601 - Fitzroy
Recruitment hospital [4] 0 0
Alfred Hospital /ID# 210350 - Melbourne
Recruitment hospital [5] 0 0
Box Hill Hospital /ID# 210599 - Melbourne
Recruitment postcode(s) [1] 0 0
2298 - Waratah
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
3065 - Fitzroy
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
3128 - 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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Iowa
Country [4] 0 0
United States of America
State/province [4] 0 0
Kansas
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Missouri
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Pennsylvania
Country [10] 0 0
Germany
State/province [10] 0 0
Sachsen
Country [11] 0 0
Germany
State/province [11] 0 0
Berlin
Country [12] 0 0
Germany
State/province [12] 0 0
Dresden
Country [13] 0 0
Germany
State/province [13] 0 0
Frankfurt
Country [14] 0 0
Germany
State/province [14] 0 0
Hamburg

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
AbbVie
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Genentech, Inc.
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Commercial sector/Industry
Name [2] 0 0
Amgen
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This dose-escalation study evaluating the safety, pharmacokinetics and preliminary efficacy
of venetoclax in combination with AMG 176 in participants with relapsed or refractory acute
myeloid leukemia (AML) and participants with Non-Hodgkin's lymphoma (NHL)/diffuse large
B-cell lymphoma (DLBCL).

This study will include a dose escalation phase to identify the maximum tolerated
dose/recommended phase 2 dose (MTD/RPTD) of venetoclax plus AMG 176 as well as a dose
expansion phase to confirm safety, explore efficacy, and confirm the suitability of the
preliminary RPTD.
Trial website
https://clinicaltrials.gov/show/NCT03797261
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
ABBVIE CALL CENTER
Address 0 0
Country 0 0
Phone 0 0
847.283.8955
Fax 0 0
Email 0 0
abbvieclinicaltrials@abbvie.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03797261