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

Leukemia, Myeloid, Acute Clinical Trial

Official title:

An Open-Label, Phase I, Dose-Escalation Study Evaluating the Safety and Tolerability of DCLL9718S in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) or DCLL9718S in Combination With Azacitidine in Patients With Previously Untreated AML Unsuitable for Intensive Induction Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03298516
• Other study ID #: GO39902
• Status: Completed
• Phase: Phase 1
• Start date: November 15, 2017
• Est. completion date: July 16, 2019

Study information

• Verified date: November 2019
• Source: Genentech, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: July 16, 2019
• Est. primary completion date: July 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• DCLL9718S
DCLL9718S will be administered as per the schedule specified in the respective arm.
• Azacitidine
Azacitidine will be administered as per the schedule specified in the respective arm.

Locations

Country	Name	City	State
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	Jewish General Hospital / McGill University	Montreal	Quebec
Canada	Princess Margaret Hospital; Department of Med Oncology	Toronto	Ontario
United States	University of Colorado Hospital - Anschutz Cancer Pavilion	Aurora	Colorado
United States	City of Hope	Duarte	California
United States	MD Anderson Cancer Center	Houston	Texas
United States	Yale School of Medicine	New Haven	Connecticut
United States	Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of participants With Adverse Events (AEs)		Baseline up to end of study (up to approximately 3 years)
Primary	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)
Primary	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)
Primary	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	Serum Concentration of DCLL9718S		up to 3 years
Secondary	Plasma Concentration of Azacitidine		up to 3 years
Secondary	Area Under the Concentration-Time Curve (AUC) of DCLL9718S		up to 3 years
Secondary	Maximum Plasma Concentration Observed (Cmax) of DCLL9718S		up to 3 years
Secondary	Total Clearance of DCLL9718S		up to 3 years
Secondary	Terminal Half-Life (t1/2) of DCLL9718S		up to 3 years
Secondary	Volume of Distribution Under Steady-State (Vss) of DCLL9718S		up to 3 years
Secondary	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)
Secondary	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)
Secondary	Overall Survival		From the date of first treatment to the date of death from any cause (up to approximately 3 years)
Secondary	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)
Secondary	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)
Secondary	Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S		Baseline up to end of study (up to approximately 3 years)