An Efficacy and Safety Study of Decitabine (DACOGEN) Plus Talacotuzumab (JNJ-56022473; Anti CD123) Versus Decitabine (DACOGEN) Alone in Participants With Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy

A Randomized Phase 2/3 Study of DACOGEN® (Decitabine) Plus Talacotuzumab (JNJ-56022473; Anti CD123) Versus DACOGEN (Decitabine) Alone in Patients With AML Who Are Not Candidates for Intensive Chemotherapy

The primary objective of study Part A is to assess the safety of talacotuzumab (formerly CSL362) monotherapy and confirm the recommended Phase 2 dose (RP2D) in participants with acute myeloid leukemia (AML) for whom experimental therapy is appropriate. The primary objective of study Part B are to assess complete response (CR) rate and overall survival (OS) in participants with AML who are not eligible for intense induction chemotherapy and who are randomly assigned to receive decitabine plus talacotuzumab at the RP2D or decitabine alone.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: Decitabine 20 mg/m^2; Drug: Talacotuzumab 9 mg/kg

Detailed Description

This is a 2-part, open-label, multicenter, Phase 2/3 study conducted in participants with AML who are suitable for experimental therapy (Part A) and in participants with untreated AML who are not eligible for intense induction chemotherapy or hematopoeitic stem cell transplantation (HSCT) (Part B). In Study Part A, the safety, pharmacokinetic (PK) and pharmacodynamic (PD) profile will be assessed to confirm the RP2D of 9 milligram per kilogram (mg/kg) talacotuzumab. In Study Part B, participants will be randomized in a 1:1 ratio into either decitabine + talacotuzumab (arm 1) or decitabine alone (arm 2). Blood and bone marrow sampling will be done in Part A and B for disease assessment, PK, PD, and biomarkers will be collected in all participants. Safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 326
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Herston, Australia
  • Melbourne, Australia
  • Perth, Australia
  • South Woodville, Australia
  • Woolloongabba, Australia
• Belgium
  • Antwerp, Belgium
  • Hasselt, Belgium
  • Leuven, Belgium
  • Liege, Belgium
  • Mons, Belgium
  • Turnhout, Belgium
  • Wilrijk, Belgium
• France
  • Grenoble Cedex 9, France
  • Lyon Cedex 08, France
  • Marseille, France
  • Montpellier, France
  • Nantes Cedex 2, France
  • Paris Cedex 10, France
  • Toulouse Cedex 9, France
• Germany
  • Dresden, Germany
  • Düsseldorf, Germany
  • Essen, Germany
  • Frankfurt/Main, Germany
  • Hamburg, Germany
  • München, Germany
  • Münster, Germany
  • Ulm, Germany
  • Würzburg, Germany
• Israel
  • Haifa, Israel
  • Jerusalem, Israel
  • Ramat Gan, Israel
  • Tel Aviv, Israel
• Korea, Republic of
  • Busan, Korea, Republic of
  • Daegu, Korea, Republic of
  • Hwasun Gun, Korea, Republic of
  • Seoul, Korea, Republic of
• Poland
  • Katowice, Poland
  • Krakow, Poland
  • Lodz, Poland
  • Lublin, Poland
  • Warszawa, Poland
• Russian Federation
  • Chelyabinsk, Russian Federation
  • Dzerzhinsk, Russian Federation
  • Ekaterinburg, Russian Federation
  • Moscow, Russian Federation
  • Nizhny Novgorod, Russian Federation
  • Ryazan, Russian Federation
  • Samara, Russian Federation
• Spain
  • Badalona, Barcelona, Spain
  • Barcelona, Spain
  • Madrid, Spain
  • Pozuelo De Alarcon, Madrid, Spain
  • Salamanca, Spain
  • Sevilla, Spain
  • Valencia, Spain
• Sweden
  • Gothenburg, Sweden
  • Stockholm, Sweden
  • Uppsala, Sweden
  • Örebro, Sweden
• Taiwan
  • Chiayi, Taiwan
  • Taichung City, Taiwan
  • Tainan City, Taiwan
  • Taipei City, Taiwan
• Turkey
  • Ankara, Turkey
  • Atakum, Turkey
  • Istanbul, Turkey
  • Izmir, Turkey
• United Kingdom
  • Bournemouth, United Kingdom
  • Cardiff, United Kingdom
  • Wolverhampton, United Kingdom
• United States
  • California
    • Orange, California, United States
  • Colorado
    • Aurora, Colorado, United States
  • Louisiana
    • New Orleans, Louisiana, United States
  • Michigan
    • Detroit, Michigan, United States
  • New Hampshire
    • Lebanon, New Hampshire, United States
  • New York
    • New York, New York, United States
    • Rochester, New York, United States
  • South Carolina
    • Charleston, South Carolina, United States
  • Tennessee
    • Nashville, Tennessee, United States
  • Texas
    • Dallas, Texas, United States
    • Houston, Texas, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• De novo or secondary acute myeloid leukemia (AML) (post myelodysplastic syndrome [MDS] or myeloproliferative neoplasm [MPN] or after leukemogenic chemotherapy) according to WHO 2008 criteria

For Part A:

- Participants With AML: treatment naive or relapsed for whom experimental therapy is appropriate (as assessed by their treating physician)

For Part B:

• Greater than or equal to (>=) 75 years of age or >= 65 up to 75 years of age and have at least one of the following: congestive heart failure or ejection fraction less than or equal to (<=) 50 percent; creatinine greater than (>) 2 milligram per deciliter (mg/dL); dialysis or prior renal transplant; documented pulmonary disease with lung diffusing capacity for carbon monoxide (DLCO) <= 65 percent of expected, or forced expiratory volume in 1 second (FEV1) <= 65 percent of expected or dyspnea at rest requiring oxygen; eastern cooperative oncology group (ECOG) performance status of 2; prior or current malignancy that does not require concurrent treatment; unresolved infection; comorbidity that, in the Investigator's opinion, makes the participant unsuitable for intensive chemotherapy and must be documented and approved by the Sponsor before randomization
• Previously untreated AML (except: emergency leukopheresis and/or hydroxyurea during the screening phase to control hyperleukocytosis but must be discontinued at least one day prior to start of study therapy)
• Not eligible for an allogeneic hematopoietic stem cell transplantation
• ECOG Performance Status score of 0, 1 or 2
• A woman must be either: Not of childbearing potential: postmenopausal (more than [>] 45 years of age with amenorrhea for at least 12 months; If, of childbearing potential must be practicing a highly effective method of birth control
• A woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [beta-hCG]) or urine pregnancy test at screening
• A man who is sexually active with a woman of childbearing potential and has not had a vasectomy must agree to use a barrier method of birth control eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository for at least 3 months after last study treatment

Exclusion Criteria:

• Acute promyelocytic leukemia with t(15;17), or its molecular equivalent (PML-RARalpha)
• For Part B only: Known leukemic involvement or clinical symptoms of leukemic involvement of the central nervous system
• Participants who received prior treatment with a hypomethylating agent
• For Part A only: Participants who did not recover from all clinically significant toxicities (excluding alopecia and hematologic toxicities) of any previous surgery, radiotherapy, targeted therapy, or chemotherapy to less than or equal to Grade 1
• Any uncontrolled active systemic infection that requires treatment with intravenous (IV) antibiotics
• A history of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV if tested at screening
• Active systemic hepatitis infection requiring treatment or other clinically active liver disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Decitabine plus Talacotuzumab; Part A: For Cycle 1 of Part A, participants will receive talacotuzumab on Day 1. Starting from Cycle 2 of Part A, participants may receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle. Part B Arm 1: Participants will receive decitabine on Day 1, 2, 3, 4, and 5, and talacotuzumab on Day 8 and 22 of a 28-day cycle.	Drug: Decitabine 20 mg/m^2; Decitabine 20 milligram per square meter (mg/[m^2]) from Day 1, 2, 3, 4 and 5 of a 28-day cycle.; Other Names: DACOGEN; Drug: Talacotuzumab 9 mg/kg; Talacotuzumab 9 milligram per kilogram mg/kg on Day 8 and 22 of a 28-day cycle.; Other Names: CSL362
Active Comparator: Decitabine; Participants in Part B Arm 2 will receive decitabine on Day 1,2, 3, 4 and 5 of a 28-day cycle.	Drug: Decitabine 20 mg/m^2; Decitabine 20 milligram per square meter (mg/[m^2]) from Day 1, 2, 3, 4 and 5 of a 28-day cycle.; Other Names: DACOGEN

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B: Percentage of Participants Who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment	Complete response rate defined as percentage of participants who achieved complete response as per modified International Working Group (IWG) criteria. CR: Bone marrow blasts less than (<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0*10^9/liter (L) (1000/micro liter [mcL]); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.	Approximately up to 2.5 years
Part B: Overall Survival	Overall Survival (OS) was defined as the time from the date of randomization to date of death from any cause. Median Overall Survival was estimated by using the Kaplan-Meier method. This endpoint is reported here for Part B only as per the planned analysis.	Approximately up to 2.5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B: Event-free Survival (EFS) Based on Investigator Assessment	EFS defined as time from randomization to treatment failure, relapse from CR/CRi, or death from any cause, whichever occurs first, per modified IWG criteria. Treatment failure: >25% absolute increase in the bone marrow blast count from baseline to present assessment (example, 20% to 46%) on bone marrow aspirate (or biopsy in case of dry tap); Relapse: Bone marrow blasts greater than equal to (>=)5%; reappearance of blasts in blood; or development of extramedullary disease; CR: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1.0*10^9/L (1000/mcL); platelet count >100*10^9/L (100 000/mcL);independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. Endpoint reported is for Part B only as per planned analysis.	Approximately up to 2.5 years
Part B: Percentage of Participants Who Achieved CR and CRi (Overall Response Rate)	Percentage of participants who achieved CR and CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0 *10^9/liter (L) (1000/ mcL); platelet count >100 *10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.	Approximately up to 2.5 years
Part B: Percentage of Participants With Complete Response (CR) Plus Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi)	Percentage of participants who achieved CR plus MRD-negative CRi were reported. MRD negativity defined as <1 blast or leukemic stem cell in 10,000 leukocytes (MRD level <10^4).CR: Bone marrow blasts less than (<)5 percent (%); absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0*10^9/liter (L) (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.	Approximately 2.5 years
Part B: Time to Best Response	Time to best response is calculated as the time from the randomization date to the first documented date for the best response for participants who achieved CR or CRi, as per modified IWG criteria. CR: Bone marrow blasts less than (<)5 %; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count greater than (>)1.0 *10^9/liter (L) (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0*10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.	Approximately 2.5 years
Part B: Duration of Response (DOR) Based on Investigator Assessment	DOR defined as number of weeks from documented best response (CR or CRi) for participants who achieved CR or CRi to relapse, death due to relapse, date of censoring. As per modified IWG criteria: CR: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease;absolute neutrophil count >1.0*10^9/L (1000/mcL); platelet count >100*10^9/L (100 000/mcL); independence of red cell transfusions; CRi: Bone marrow blasts <5 %; absence of blasts with Auer rods; absence of extramedullary disease; residual neutropenia <1.0* 10^9/L (1000/mcL) or thrombocytopenia <100*10^9/L (100 000/mcL); independence of red cell transfusions. This endpoint is reported here for Part B only as per the planned analysis.	Approximately 2.5 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Peipert JD, Efficace F, Pierson R, Loefgren C, Cella D, He J. Patient-reported outcomes predict overall survival in older patients with acute myeloid leukemia. J Geriatr Oncol. 2022 Sep;13(7):935-939. doi: 10.1016/j.jgo.2021.09.007. Epub 2021 Sep 11.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2015
• Primary Completion (Actual): January 25, 2018
• Study Completion (Actual): January 25, 2018

Study Registration Dates

• First Submitted: April 29, 2015
• First Submitted That Met QC Criteria: June 10, 2015
• First Posted (Estimate): June 15, 2015

Study Record Updates

• Last Update Posted (Actual): March 19, 2019
• Last Update Submitted That Met QC Criteria: March 11, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Decitabine; Leukemia, myeloid, acute; DACOGEN; JNJ-56022473; CLS362
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: CR107273; 56022473AML2002 (Other Identifier: Janssen Research & Development, LLC); 2015-001611-12 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No