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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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ClinicalTrials.gov Identifier: NCT03298516
Recruitment Status : Completed
First Posted : October 2, 2017
Last Update Posted : November 19, 2019
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

Tracking Information
First Submitted Date  ICMJE September 27, 2017
First Posted Date  ICMJE October 2, 2017
Last Update Posted Date November 19, 2019
Actual Study Start Date  ICMJE November 15, 2017
Actual Primary Completion Date July 16, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 27, 2017)
  • Percentage of participants With Adverse Events (AEs) [ Time Frame: Baseline up to end of study (up to approximately 3 years) ]
  • 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) ]
  • 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) ]
  • 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) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 27, 2017)
  • Serum Concentration of DCLL9718S [ Time Frame: up to 3 years ]
  • Plasma Concentration of Azacitidine [ Time Frame: up to 3 years ]
  • Area Under the Concentration-Time Curve (AUC) of DCLL9718S [ Time Frame: up to 3 years ]
  • Maximum Plasma Concentration Observed (Cmax) of DCLL9718S [ Time Frame: up to 3 years ]
  • Total Clearance of DCLL9718S [ Time Frame: up to 3 years ]
  • Terminal Half-Life (t1/2) of DCLL9718S [ Time Frame: up to 3 years ]
  • Volume of Distribution Under Steady-State (Vss) of DCLL9718S [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: From the date of first response to the earliest recurrence or disease progression (up to approximately 3 years) ]
  • Overall Survival [ Time Frame: 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 [ 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) ]
  • 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) ]
  • Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S [ Time Frame: Baseline up to end of study (up to approximately 3 years) ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia, Myeloid, Acute
Intervention  ICMJE
  • 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 Name: Vidaza
Study Arms  ICMJE
  • 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.
    Intervention: Drug: DCLL9718S
  • 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.
    Interventions:
    • Drug: DCLL9718S
    • Drug: Azacitidine
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 17, 2019)
19
Original Estimated Enrollment  ICMJE
 (submitted: September 27, 2017)
110
Actual Study Completion Date  ICMJE July 16, 2019
Actual Primary Completion Date July 16, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries Korea, Republic of
 
Administrative Information
NCT Number  ICMJE NCT03298516
Other Study ID Numbers  ICMJE GO39902
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Genentech, Inc.
Study Sponsor  ICMJE Genentech, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Clinical Trials Hoffmann-La Roche
PRS Account Genentech, Inc.
Verification Date November 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP