Leukemia, Myeloid, Acute
Conditions
Brief summary
This Phase Ia/Ib, open-label, multicenter study will evaluate the safety, tolerability, and preliminary efficacy of DCLL9718S as a single agent (Phase Ia, Arm A) in participants with relapsed or refractory AML or in combination with azacitidine (Phase Ib, Arm B) in participants with previously untreated AML who are not eligible for intensive induction chemotherapy. Each arm will consist of two stages: a dose-escalation stage and an expansion stage. The dose-escalation stage is designed to establish the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) for DCLL9718S alone (Arm A) or in combination with azacitidine (Arm B). The dose-expansion stage is designed to characterize the long-term safety and tolerability of DCLL9718S.
Interventions
DRUGDCLL9718S
DCLL9718S will be administered as per the schedule specified in the respective arm.
DRUGAzacitidine
Azacitidine will be administered as per the schedule specified in the respective arm.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of AML per World Health Organization (WHO) criteria (except acute promyelocytic leukemia) * Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1, or 2 * Adequate end-organ function * Willing and able to undergo a pre-treatment bone marrow aspirate and biopsy and subsequent bone marrow aspirates and biopsies during treatment Specifically for participants in Arm A: * Age greater than or equal to (\>/=) 18 years * Relapsed or refractory acute myeloid leukemia * Participants cannot have received more than two prior regimens Specifically for participants in Arm B: * Treatment-naive participants with AML who are \>/=75 years old * Treatment-naive participants unfit for induction chemotherapy for AML due to comorbidities who are \>/=65 years old
Exclusion criteria
* Diagnosis of acute promyelocytc leukemia * Prior allogeneic stem cell transplant or solid organ transplant * Active central nervous system (CNS) involvement by leukemia * History of idiopathic pulmonary fibrosis, organizing pneumonitis (for example \[e.g.\], bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis * Treatment with investigational therapy within 14 days prior to Cycle 1, Day 1 * Treatment with a monoclonal antibody within 30 days prior to Cycle 1, Day 1 * Positive for hepatitis C virus (HCV) antibody at screening * Active hepatitis B virus (HBV) infection * Known positivity for human immunodeficiency virus (HIV) * History of other malignancy within 2 years prior to screening * Family history of long QT syndrome, with a QTc interval greater than (\>) 480 millisecond (msec) at screening, or taking concurrent medications known to prolong QT/QTc interval
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of participants With Adverse Events (AEs) | Baseline up to end of study (up to approximately 3 years) |
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) | Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B) |
| MTD of DCLL9718S | Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B) |
| RP2D of DCLL9718S | Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B) |
Secondary
| Measure | Time frame |
|---|---|
| Total Clearance of DCLL9718S | up to 3 years |
| Terminal Half-Life (t1/2) of DCLL9718S | up to 3 years |
| Volume of Distribution Under Steady-State (Vss) of DCLL9718S | up to 3 years |
| Percentage of Participants With Complete Remission (CR), CR With Incomplete Blood Count Recovery (CRi), CR With Incomplete Platelet Count Recovery (CRp), and Overall Response, Assessed as per International Working Group (IWG) Criteria | From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years) |
| Serum Concentration of DCLL9718S | up to 3 years |
| Overall Survival | From the date of first treatment to the date of death from any cause (up to approximately 3 years) |
| Event-Free Survival (EFS), Assessed as per IWG Criteria | From the date of first treatment until treatment failure, relapsed from CR, CRp, or CRi, or death from any cause, whichever occurs first (up to approximately 3 years) |
| Progression-Free Survival (PFS), Assessed as per IWG Criteria | From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years) |
| Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S | Baseline up to end of study (up to approximately 3 years) |
| Duration of Response, Assessed as per IWG Criteria | From the date of first response to the earliest recurrence or disease progression (up to approximately 3 years) |
| Plasma Concentration of Azacitidine | up to 3 years |
| Area Under the Concentration-Time Curve (AUC) of DCLL9718S | up to 3 years |
| Maximum Plasma Concentration Observed (Cmax) of DCLL9718S | up to 3 years |
Countries
Canada, United States
Outcome results
None listed