Clinical trial NCT03298516: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia, Myeloid, Acute
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2017-10-02
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of participants With Adverse Events (AEs)
timeFrame: Baseline up to end of study (up to approximately 3 years)
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
measure: MTD of DCLL9718S
timeFrame: Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
measure: RP2D of DCLL9718S
timeFrame: Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
Secondary outcomes:
measure: Serum Concentration of DCLL9718S
timeFrame: up to 3 years
measure: Plasma Concentration of Azacitidine
timeFrame: up to 3 years
measure: Area Under the Concentration-Time Curve (AUC) of DCLL9718S
timeFrame: up to 3 years
measure: Maximum Plasma Concentration Observed (Cmax) of DCLL9718S
timeFrame: up to 3 years
measure: Total Clearance of DCLL9718S
timeFrame: up to 3 years
measure: Terminal Half-Life (t1/2) of DCLL9718S
timeFrame: up to 3 years
measure: Volume of Distribution Under Steady-State (Vss) of DCLL9718S
timeFrame: up to 3 years
measure: 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
timeFrame: From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years)
measure: Duration of Response, Assessed as per IWG Criteria
timeFrame: From the date of first response to the earliest recurrence or disease progression (up to approximately 3 years)
measure: Overall Survival
timeFrame: From the date of first treatment to the date of death from any cause (up to approximately 3 years)
measure: Event-Free Survival (EFS), Assessed as per IWG Criteria
timeFrame: 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)
measure: Progression-Free Survival (PFS), Assessed as per IWG Criteria
timeFrame: From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years)
measure: Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S
timeFrame: Baseline up to end of study (up to approximately 3 years)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital - Anschutz Cancer Pavilion
state: Colorado
city: New Haven
country: United States
facility: Yale School of Medicine
state: Connecticut
city: New York
country: United States
facility: Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta Hospital
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Hospital; Department of Med Oncology
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital / McGill University
state: Quebec
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.