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

NCT ID: NCT02472145

Last Updated: 2019-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 326 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-08-04
• Study Completion Date: 2018-01-25

Brief Summary

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.

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.

Conditions

Leukemia, Myeloid, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Decitabine 20 mg/m^2

Intervention Type: DRUG

Decitabine 20 milligram per square meter (mg/\[m\^2\]) from Day 1, 2, 3, 4 and 5 of a 28-day cycle.

Talacotuzumab 9 mg/kg

Intervention Type: DRUG

Talacotuzumab 9 milligram per kilogram mg/kg on Day 8 and 22 of a 28-day cycle.

Decitabine

Participants in Part B Arm 2 will receive decitabine on Day 1,2, 3, 4 and 5 of a 28-day cycle.

Group Type: ACTIVE_COMPARATOR

Decitabine 20 mg/m^2

Intervention Type: DRUG

Decitabine 20 milligram per square meter (mg/\[m\^2\]) from Day 1, 2, 3, 4 and 5 of a 28-day cycle.

Interventions

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.

Intervention Type: DRUG

Talacotuzumab 9 mg/kg

Talacotuzumab 9 milligram per kilogram mg/kg on Day 8 and 22 of a 28-day cycle.

Intervention Type: DRUG

Other Intervention Names

DACOGEN; CSL362

Eligibility Criteria

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

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Orange, California, United States

Aurora, Colorado, United States

New Orleans, Louisiana, United States

Detroit, Michigan, United States

Lebanon, New Hampshire, United States

New York, New York, United States

Rochester, New York, United States

Charleston, South Carolina, United States

Nashville, Tennessee, United States

Dallas, Texas, United States

Houston, Texas, United States

Herston, , Australia

Melbourne, , Australia

Perth, , Australia

South Woodville, , Australia

Woolloongabba, , Australia

Antwerp, , Belgium

Hasselt, , Belgium

Leuven, , Belgium

Liège, , Belgium

Mons, , Belgium

Turnhout, , Belgium

Wilrijk, , Belgium

Grenoble, , France

Lyon, , France

Marseille, , France

Montpellier, , France

Nantes, , France

Paris, , France

Toulouse, , France

Dresden, , Germany

Düsseldorf, , Germany

Essen, , Germany

Frankfurt am Main, , Germany

Hamburg, , Germany

München, , Germany

Münster, , Germany

Ulm, , Germany

Würzburg, , Germany

Haifa, , Israel

Jerusalem, , Israel

Ramat Gan, , Israel

Tel Aviv, , Israel

Katowice, , Poland

Krakow, , Poland

Lodz, , Poland

Lublin, , Poland

Warsaw, , Poland

Chelyabinsk, , Russia

Dzerzhinsk, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Ryazan, , Russia

Samara, , Russia

Yekaterinburg, , Russia

Busan, , South Korea

Daegu, , South Korea

Hwasun Gun, , South Korea

Seoul, , South Korea

Badalona, Barcelona, , Spain

Barcelona, , Spain

Madrid, , Spain

Pozuelo de Alarcon, Madrid, , Spain

Salamanca, , Spain

Seville, , Spain

Valencia, , Spain

Gothenburg, , Sweden

Örebro, , Sweden

Stockholm, , Sweden

Uppsala, , Sweden

Chiayi City, , Taiwan

Taichung, , Taiwan

Tainan City, , Taiwan

Taipei, , Taiwan

Ankara, , Turkey (Türkiye)

Atakum, , Turkey (Türkiye)

Istanbul, , Turkey (Türkiye)

Izmir, , Turkey (Türkiye)

Bournemouth, , United Kingdom

Cardiff, , United Kingdom

Wolverhampton, , United Kingdom

Countries

United States; Australia; Belgium; France; Germany; Israel; Poland; Russia; South Korea; Spain; Sweden; Taiwan; Turkey (Türkiye); United Kingdom

References

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.

Reference Type: DERIVED

PMID: 34521609 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

56022473AML2002

Identifier Type: OTHER

Identifier Source: secondary_id

2015-001611-12

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CR107273

Identifier Type: -

Identifier Source: org_study_id