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

NCT03298516 | Completed Phase 1 FDA Drug

• 1 other identifier: GO39902
• Study Type: interventional
• Target: 19
• Locations: 2 countries
• Sites: 8

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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (4)

• Percentage of participants With Adverse Events (AEs)

  Baseline up to end of study (up to approximately 3 years)

• Percentage of Participants With Dose-Limiting Toxicities (DLTs)

  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

  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

  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 (13)

• Serum Concentration of DCLL9718S

  up to 3 years

• Plasma Concentration of Azacitidine

  up to 3 years

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

  up to 3 years

• Maximum Plasma Concentration Observed (Cmax) of DCLL9718S

  up to 3 years

• Total Clearance of DCLL9718S

  up to 3 years

Study Arms (2)

Arm A: DCLL9718S

EXPERIMENTAL

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

Arm B: DCLL9718S and Azacitidine

EXPERIMENTAL

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

DCLL9718S DRUG

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

Arm A: DCLL9718S; Arm B: DCLL9718S and Azacitidine

Azacitidine DRUG

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

Also known as: Vidaza

Arm B: DCLL9718S and Azacitidine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (8)

City of Hope

Duarte, California, 91010, United States

Location

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Yale School of Medicine

New Haven, Connecticut, 06510, United States

Location

Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749

New York, New York, 10032, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 1C9, Canada

Location

Princess Margaret Hospital; Department of Med Oncology

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital / McGill University

Montreal, Quebec, H3T 1E2, Canada

Location

Related Publications (1)

• 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.

  PMID: 33617672 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

DCLL9718S; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 27, 2017
• First Posted: October 2, 2017
• Study Start: November 15, 2017
• Primary Completion: July 16, 2019
• Study Completion: July 16, 2019
• Last Updated: November 19, 2019

Record last verified: 2019-11

Locations

US (5); CA (3)