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

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: DCLL9718S; Drug: Azacitidine

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1C9
      • University of Alberta Hospital
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Hospital; Department of Med Oncology
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital / McGill University
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital - Anschutz Cancer Pavilion
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749
  • Texas
    • Houston, Texas, United States, 77030
      • Md Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: DCLL9718S; 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.	Drug: DCLL9718S; DCLL9718S will be administered as per the schedule specified in the respective arm.
Experimental: Arm B: DCLL9718S and Azacitidine; 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.	Drug: DCLL9718S; DCLL9718S will be administered as per the schedule specified in the respective arm.; Drug: Azacitidine; Azacitidine will be administered as per the schedule specified in the respective arm.; Other Names: Vidaza

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Time Frame
Serum Concentration of DCLL9718S	up to 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
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)
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)
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)

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Publications and helpful links

General Publications

• Daver N, Salhotra A, Brandwein JM, Podoltsev NA, Pollyea DA, Jurcic JG, Assouline S, Yee K, Li M, Pourmohamad T, Samineni D, Sumiyoshi T, Vaze A, Dere RC, Ma C, Cooper J. A Phase I dose-escalation study of DCLL9718S, an antibody-drug conjugate targeting C-type lectin-like molecule-1 (CLL-1) in patients with acute myeloid leukemia. Am J Hematol. 2021 May 1;96(5):E175-E179. doi: 10.1002/ajh.26136. Epub 2021 Mar 11. No abstract available.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2017
• Primary Completion (Actual): July 16, 2019
• Study Completion (Actual): July 16, 2019

Study Registration Dates

• First Submitted: September 27, 2017
• First Submitted That Met QC Criteria: September 27, 2017
• First Posted (Actual): October 2, 2017

Study Record Updates

• Last Update Posted (Actual): November 19, 2019
• Last Update Submitted That Met QC Criteria: November 18, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: GO39902

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No