Clinical trial NCT02472145: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Leukemia, Myeloid, Acute
Keywords: Leukemia, myeloid, acute
DACOGEN
Decitabine
JNJ-56022473
CLS362
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2015-06-15
Enrollment: 326
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Part B: Percentage of Participants Who Achieved Complete Response (Complete Response Rate) Based on Investigator Assessment
timeFrame: Approximately up to 2.5 years
measure: Part B: Overall Survival
timeFrame: Approximately up to 2.5 years
Secondary outcomes:
measure: Part B: Event-free Survival (EFS) Based on Investigator Assessment
timeFrame: Approximately up to 2.5 years
measure: Part B: Percentage of Participants Who Achieved CR and CRi (Overall Response Rate)
timeFrame: Approximately up to 2.5 years
measure: Part B: Percentage of Participants With Complete Response (CR) Plus Minimal Residual Disease (MRD) Negative Complete Response With Incomplete Recovery (CRi)
timeFrame: Approximately 2.5 years
measure: Part B: Time to Best Response
timeFrame: Approximately 2.5 years
measure: Part B: Duration of Response (DOR) Based on Investigator Assessment
timeFrame: Approximately 2.5 years
Other outcomes:
Locations:
city: Orange
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: New Orleans
country: United States
state: Louisiana
city: Detroit
country: United States
state: Michigan
city: Lebanon
country: United States
state: New Hampshire
city: New York
country: United States
state: New York
city: Rochester
country: United States
state: New York
city: Charleston
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Dallas
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Herston
country: Australia
city: Melbourne
country: Australia
city: Perth
country: Australia
city: South Woodville
country: Australia
city: Woolloongabba
country: Australia
city: Antwerp
country: Belgium
city: Hasselt
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Mons
country: Belgium
city: Turnhout
country: Belgium
city: Wilrijk
country: Belgium
city: Grenoble Cedex 9
country: France
city: Lyon Cedex 08
country: France
city: Marseille
country: France
city: Montpellier
country: France
city: Nantes Cedex 2
country: France
city: Paris Cedex 10
country: France
city: Toulouse Cedex 9
country: France
city: Dresden
country: Germany
city: Düsseldorf
country: Germany
city: Essen
country: Germany
city: Frankfurt/Main
country: Germany
city: Hamburg
country: Germany
city: München
country: Germany
city: Münster
country: Germany
city: Ulm
country: Germany
city: Würzburg
country: Germany
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Ramat Gan
country: Israel
city: Tel Aviv
country: Israel
city: Busan
country: Korea, Republic of
city: Daegu
country: Korea, Republic of
city: Hwasun Gun
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Katowice
country: Poland
city: Krakow
country: Poland
city: Lodz
country: Poland
city: Lublin
country: Poland
city: Warszawa
country: Poland
city: Chelyabinsk
country: Russian Federation
city: Dzerzhinsk
country: Russian Federation
city: Ekaterinburg
country: Russian Federation
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: Ryazan
country: Russian Federation
city: Samara
country: Russian Federation
city: Badalona, Barcelona
country: Spain
city: Barcelona
country: Spain
city: Madrid
country: Spain
city: Pozuelo De Alarcon, Madrid
country: Spain
city: Salamanca
country: Spain
city: Sevilla
country: Spain
city: Valencia
country: Spain
city: Gothenburg
country: Sweden
city: Stockholm
country: Sweden
city: Uppsala
country: Sweden
city: Örebro
country: Sweden
city: Chiayi
country: Taiwan
city: Taichung City
country: Taiwan
city: Tainan City
country: Taiwan
city: Taipei City
country: Taiwan
city: Ankara
country: Turkey
city: Atakum
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Bournemouth
country: United Kingdom
city: Cardiff
country: United Kingdom
city: Wolverhampton
country: United Kingdom
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: 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.