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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 : Recruiting
First Posted : October 2, 2017
Last Update Posted : April 2, 2018
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.

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.

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid, Acute Drug: DCLL9718S Drug: Azacitidine Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 110 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 15, 2017
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : September 30, 2023


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 Name: Vidaza



Primary Outcome Measures :
  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 Outcome Measures :
  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) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03298516


Contacts
Contact: Reference Study ID Number: GO39902 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
United States, Colorado
University of Colorado Hospital - Anschutz Cancer Pavilion Recruiting
Aurora, Colorado, United States, 80045
United States, Connecticut
Yale School of Medicine Recruiting
New Haven, Connecticut, United States, 06510
United States, New York
Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749 Recruiting
New York, New York, United States, 10032
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Hoffmann-La Roche

Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT03298516     History of Changes
Other Study ID Numbers: GO39902
First Posted: October 2, 2017    Key Record Dates
Last Update Posted: April 2, 2018
Last Verified: March 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Enzyme Inhibitors