Back to resultsA 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
Primary Purpose
Leukemia, Myeloid, Acute
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
DCLL9718S
Azacitidine
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Acute
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
Sites / Locations
- City of Hope
- University of Colorado Hospital - Anschutz Cancer Pavilion
- Yale School of Medicine
- Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749
- MD Anderson Cancer Center
- University of Alberta Hospital
- Princess Margaret Hospital; Department of Med Oncology
- Jewish General Hospital / McGill University
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Arm A: DCLL9718S
Arm B: DCLL9718S and Azacitidine
Arm 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.
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.
Outcomes
Primary Outcome Measures
Percentage of participants With Adverse Events (AEs)
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
MTD of DCLL9718S
RP2D of DCLL9718S
Secondary Outcome Measures
Serum Concentration of DCLL9718S
Plasma Concentration of Azacitidine
Area Under the Concentration-Time Curve (AUC) of DCLL9718S
Maximum Plasma Concentration Observed (Cmax) of DCLL9718S
Total Clearance of DCLL9718S
Terminal Half-Life (t1/2) of DCLL9718S
Volume of Distribution Under Steady-State (Vss) of DCLL9718S
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
Duration of Response, Assessed as per IWG Criteria
Overall Survival
Event-Free Survival (EFS), Assessed as per IWG Criteria
Progression-Free Survival (PFS), Assessed as per IWG Criteria
Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03298516
Brief Title
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
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
November 15, 2017 (Actual)
Primary Completion Date
July 16, 2019 (Actual)
Study Completion Date
July 16, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Genentech, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Acute
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: DCLL9718S
Arm Type
Experimental
Arm 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.
Arm Title
Arm B: DCLL9718S and Azacitidine
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
DCLL9718S
Intervention Description
DCLL9718S will be administered as per the schedule specified in the respective arm.
Intervention Type
Drug
Intervention Name(s)
Azacitidine
Other Intervention Name(s)
Vidaza
Intervention Description
Azacitidine will be administered as per the schedule specified in the respective arm.
Primary Outcome Measure Information:
Title
Percentage of participants With Adverse Events (AEs)
Time Frame
Baseline up to end of study (up to approximately 3 years)
Title
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time Frame
Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
Title
MTD of DCLL9718S
Time Frame
Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
Title
RP2D of DCLL9718S
Time Frame
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 Measure Information:
Title
Serum Concentration of DCLL9718S
Time Frame
up to 3 years
Title
Plasma Concentration of Azacitidine
Time Frame
up to 3 years
Title
Area Under the Concentration-Time Curve (AUC) of DCLL9718S
Time Frame
up to 3 years
Title
Maximum Plasma Concentration Observed (Cmax) of DCLL9718S
Time Frame
up to 3 years
Title
Total Clearance of DCLL9718S
Time Frame
up to 3 years
Title
Terminal Half-Life (t1/2) of DCLL9718S
Time Frame
up to 3 years
Title
Volume of Distribution Under Steady-State (Vss) of DCLL9718S
Time Frame
up to 3 years
Title
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
Time Frame
From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years)
Title
Duration of Response, Assessed as per IWG Criteria
Time Frame
From the date of first response to the earliest recurrence or disease progression (up to approximately 3 years)
Title
Overall Survival
Time Frame
From the date of first treatment to the date of death from any cause (up to approximately 3 years)
Title
Event-Free Survival (EFS), Assessed as per IWG Criteria
Time Frame
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)
Title
Progression-Free Survival (PFS), Assessed as per IWG Criteria
Time Frame
From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years)
Title
Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S
Time Frame
Baseline up to end of study (up to approximately 3 years)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
University of Colorado Hospital - Anschutz Cancer Pavilion
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Yale School of Medicine
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Alberta Hospital
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1C9
Country
Canada
Facility Name
Princess Margaret Hospital; Department of Med Oncology
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Facility Name
Jewish General Hospital / McGill University
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3T 1E2
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
33617672
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.
Results Reference
derived
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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
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