Acute Myeloid Leukemia, Diffuse Large B-cell Lymphoma, Non-Hodgkin's Lymphoma
Conditions
Keywords
Acute Myeloid Leukemia, Non-Hodgkin's Lymphoma, Cancer, Venetoclax, AMG 176, diffuse large B-cell lymphoma (DLBCL)
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.
Interventions
DRUGVenetoclax
tablet, oral
DRUGAMG 176
solution, intravenous
Sponsors
Genentech, Inc.
Amgen
AbbVie
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RPTD) for Venetoclax + AMG 176 | Up to 28 days after first dose of study drug in a dose-escalation phase | The MTD and/or RPTD of venetoclax and of AMG 176 will be determined during the dose escalation phase of the study. |
| Number of Participants With Adverse Events | 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). | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ORR for Participants with NHL | Up to approximately 2 years from last subject first dose | ORR is defined as the percentage of participants with documented CR + PR based on Lugano criteria for NHL. |
| Maximum Plasma Concentration (Cmax) of Venetoclax | Up to approximately 28 days after first dose of study drug | Maximum observed plasma concentration (Cmax) of venetoclax. |
| Time to Maximum Observed Plasma Concentration (Tmax) of Venetoclax | Up to approximately 28 days after first dose of study drug | Time to maximum plasma concentration (Tmax) of Venetoclax. |
| AUC of Venetoclax | Up to approximately 28 days after first dose of study drug | Area under the plasma concentration-time curve (AUC) of venetoclax. |
| Composite Complete Remission Rate (CRc) for Participants with AML | Up to approximately 2 years from last subject first dose | CRc rate is defined as CR + CRi (CR with incomplete blood count recovery). |
| Half-life (t1/2) of AMG 176 | Approximately 16 days after first dose of study drug | Terminal phase elimination half-life (t1/2) |
| AUC of AMG 176 | Approximately 16 days after first dose of study drug | Area Under the Plasma Concentration-time Curve (AUC) of AMG 176 |
| Clearance (CL) of AMG 176 | Approximately 16 days after first dose of study drug | Clearance (CL) is defined the volume of plasma cleared of the drug per unit time. |
| Maximum Plasma Concentration (Cmax) of AMG 176 | Up to approximately 16 days after first dose of study drug | Maximum observed plasma concentration (Cmax) of AMG 176 |
| Objective Response Rate (ORR) for Participants with AML | Up to approximately 2 years from last subject first dose | 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 |
Countries
Australia, Germany, United States
Outcome results
None listed