A Study of DCLL9718S in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) or DCLL9718S in Combination With Azacitidine in Participants With Previously Untreated AML Unsuitable for Intensive Induction Chemotherapy

Genentech

Status and phase: Completed; Phase 1

Conditions: Leukemia, Myeloid, Acute

Treatments: Drug: DCLL9718S; Drug: Azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT03298516

GO39902

Details and patient eligibility

About

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.

Enrollment: 19 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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19 participants in 2 patient groups

Arm A: DCLL9718S

Experimental group

Description:

Participants will receive escalating doses of DCLL9718S intravenously (IV) in each 21-day cycle to determine MTD and RP2D in dose-escalation stage followed by DCLL9718S IV at RP2D in each 21-day cycle in dose-expansion stage until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.

Treatment:

Drug: DCLL9718S

Arm B: DCLL9718S and Azacitidine

Experimental group

Description:

Participants will receive escalating doses of DCLL9718S (starting dose: at least one dose level below a completed and tolerated DCLL9718S monotherapy in Arm A) IV in each 28-day cycle and azacitidine 75 milligrams per square meter (mg/m\^2) subcutaneously (SC) or IV on Days 1-7 of each 28-day cycle to determine MTD and RP2D of DCLL9718S in dose-escalation stage followed by DCLL9718S IV at RP2D in each 28-day cycle and azacitidine 75 mg/m\^2 SC or IV on Days 1-7 of each 28-day cycle in dose-expansion stage until disease progression, unacceptable toxicity, or any other discontinuation criteria are met. Azacitidine may also be given on Days 1-5 and Days 8-9 depending on institutional preference.

Treatment:

Drug: DCLL9718S

Drug: Azacitidine