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CompletedNCT03298516Updated Nov 19, 2019

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

A Phase 1 interventional study of DCLL9718S and Azacitidine in Leukemia, Myeloid, Acute, sponsored by Genentech, Inc.. Completed at 8 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-11-19.

Sponsored by Genentech, Inc. · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
19
Allocation
Non-randomized
Ages
18 Years and older
Sex
All
01

Study 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.

02

Conditions studied

03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
19 participants (actual)

Study arms

  • 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

  • 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 · Drug: Azacitidine

Interventions

  • DrugDCLL9718S

    DCLL9718S will be administered as per the schedule specified in the respective arm.

  • DrugAzacitidine

    Azacitidine will be administered as per the schedule specified in the respective arm.

    Also known as: Vidaza

05

What researchers measure

Primary outcomes

  1. Percentage of participants With Adverse Events (AEs)

    Time frame: Baseline up to end of study (up to approximately 3 years)

  2. 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)

  3. 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)

  4. 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 outcomes

  1. Serum Concentration of DCLL9718S

    Time frame: up to 3 years

  2. Plasma Concentration of Azacitidine

    Time frame: up to 3 years

  3. Area Under the Concentration-Time Curve (AUC) of DCLL9718S

    Time frame: up to 3 years

  4. Maximum Plasma Concentration Observed (Cmax) of DCLL9718S

    Time frame: up to 3 years

  5. Total Clearance of DCLL9718S

    Time frame: up to 3 years

  6. Terminal Half-Life (t1/2) of DCLL9718S

    Time frame: up to 3 years

  7. Volume of Distribution Under Steady-State (Vss) of DCLL9718S

    Time frame: up to 3 years

  8. 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)

  9. 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)

  10. Overall Survival

    Time frame: From the date of first treatment to the date of death from any cause (up to approximately 3 years)

  11. 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)

  12. 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)

  13. Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S

    Time frame: Baseline up to end of study (up to approximately 3 years)

06

Study locations

8 sites
  • City of Hope
    Duarte, California 91010, United States
  • University of Colorado Hospital - Anschutz Cancer Pavilion
    Aurora, Colorado 80045, United States
  • Yale School of Medicine
    New Haven, Connecticut 06510, United States
  • Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749
    New York, New York 10032, United States
  • MD Anderson Cancer Center
    Houston, Texas 77030, United States
  • University of Alberta Hospital
    Edmonton, Alberta T6G 1C9, Canada
  • Princess Margaret Hospital; Department of Med Oncology
    Toronto, Ontario M5G 2M9, Canada
  • Jewish General Hospital / McGill University
    Montreal, Quebec H3T 1E2, Canada
07

References and documents

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. PubMed 33617672 ↗
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Registry details

Key details

Study ID
NCT03298516
Lead sponsor
Genentech, Inc.
Responsible party
Sponsor
First posted
Oct 2, 2017
Start date
Nov 15, 2017
Primary completion
Jul 16, 2019
Completion
Jul 16, 2019
Last update
Nov 19, 2019

Study contacts

Clinical Trials
study director · Hoffmann-La Roche

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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