Clinical trial NCT03011034: Study to Separately Evaluate the Activity of Talacotuzumab (JNJ-56022473) or Daratumumab in Transfusion-Dependent Participants With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) Who Are Relapsed or Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
Official title: A Phase 2 Proof-of-Concept Study to Separately Evaluate the Activity of Talacotuzumab (JNJ-56022473) or Daratumumab in Transfusion-Dependent Subjects With Low or Intermediate-1 Risk Myelodysplastic Syndromes (MDS) Who Are Relapsed or Refractory to Erythropoiesis-Stimulating Agent (ESA) Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Myelodysplastic Syndromes
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2017-01-05
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The main purpose of the study is to evaluate the efficacy (transfusion independence \[TI\]) of talacotuzumab (JNJ-56022473) or daratumumab in transfusion-dependent participants with low or intermediate-1 risk Myelodysplastic Syndrome (MDS) whose disease has relapsed during treatment with or is refractory to Erythropoiesis-Stimulating Agent (ESAs).

Detailed description: This is a multicenter, randomized (study drug assigned by chance), open-label (participants and researchers are aware of the treatment participants are receiving) study to evaluate the safety and efficacy of talacotuzumab or daratumumab. Approximately 60 participants (30 to receive talacotuzumab and 30 to receive daratumumab) will be enrolled and then assigned randomly on a 1:1 basis to receive either talacotuzumab or daratumumab. The study consists of: a Screening Phase of up to 28 days during which participant eligibility will be reviewed and approved by the sponsor prior to randomization, a Treatment Phase that will extend from the first dose on Cycle 1 Day 1 until study drug discontinuation, and a Post-treatment Follow up Phase beginning once the participant discontinues talacotuzumab or daratumumab. Study drugs will continue to be administered until disease progression, lack of response, unacceptable toxicity, withdrawal of consent, or study end. Safety will be monitored throughout the study. The talacotuzumab arm of the study is closed for enrollment.

Eligibility criteria: Inclusion Criteria:

* Myelodysplastic Syndrome (MDS) according to World Health Organization (WHO) criteria confirmed by bone marrow aspirate and biopsy within 12 weeks prior to first dose. A local laboratory report from this diagnostic bone marrow aspirate and biopsy must be approved by the sponsor
* International Prognostic Scoring System (IPSS) low risk or intermediate-1 risk MDS
* Red blood cell (RBC) transfusion dependent, 1) Received at least 4 units of RBCs over any 8 consecutive weeks during the 16 weeks prior to randomization, 2) Pretransfusion Hb must have been less than or equal to (\<=)9.0 gram per deciliter (g/dL)
* Adequate iron stores, defined as transferrin saturation greater than 20 percent (%) and serum ferritin greater than 400 nanogram per Milliliter (ng/mL), measured within the screening period, or adequate iron stores as demonstrated by recent (within 12 weeks prior to first dose) bone marrow examination with iron stain
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

* Known allergies, hypersensitivity, or intolerance to talacotuzumab and daratumumab or their excipients
* Received any chemotherapy, immunomodulatory or immunosuppressive therapy, corticosteroids (greater than \[\>\]30 milligram per day \[mg/day\] prednisone or equivalent) within 28 days prior to randomization
* Received other treatments for MDS within 28 days prior to first dose (example \[eg\], azacitidine, decitabine, lenalidomide, Erythropoiesis-Stimulating Agent (ESA) (8 weeks for long-acting ESAs)
* History of hematopoietic stem cell transplant
* Del(5q) karyotype unless treatment with lenalidomide has failed. Failure is defined as either: 1) having received at least 3 months of lenalidomide treatment without RBC transfusion benefit (International Working Group \[IWG\] 2006); 2) progression or relapse after hematologic improvement with lenalidomide (IWG 2006); 3) discontinuation of lenalidomide due to toxicity; or 4) unable to receive lenalidomide due to a contraindication. Source documentation for lenalidomide treatment failure must be verified by the sponsor

Primary outcomes:
measure: Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 8 Weeks
timeFrame: Up to 2 years
Secondary outcomes:
measure: Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 24 Weeks
timeFrame: Up to 2 years
measure: Time to Transfusion Independence (TI)
timeFrame: Up to 2 years
measure: Duration of Transfusion Independence (TI)
timeFrame: Up to 2 years
measure: Percentage of Participants Who Met IWG Criteria for Transfusion Reduction
timeFrame: Up to 2 years
measure: Percentage of Participants With at Least One Dose of Myeloid Growth Factors Usage
timeFrame: Up to 2 years
measure: Percentage of Participants With Hematologic Improvement (HI) Per IWG 2006 by Investigator Assessment
timeFrame: Up to 2 years
measure: Percentage of Participants With Complete Remission (CR) and Marrow CR
timeFrame: Up to 2 years
measure: Percentage of Participants With Partial Remission (PR)
timeFrame: Up to 2 years
measure: Percentage of Participants With Cytogenetic Response
timeFrame: Up to 2 years
measure: Overall Survival
timeFrame: Up to 2 years
measure: Time to Progression to Acute Myeloid Leukemia (AML)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School Of Medicine
state: Missouri
city: Philadelphia
country: United States
facility: University of Pennsylvania Abramson Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas, MD Anderson Cancer Center
state: Texas
city: Antwerp
country: Belgium
facility: ZNA Stuivenberg
city: Kortrijk
country: Belgium
facility: Az Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Turnhout
country: Belgium
facility: AZ Turnhout
city: Bologna
country: Italy
facility: Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
city: Firenze
country: Italy
facility: Azienda Ospedaliero Universitaria Careggi
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Pad. Marcora
city: Rozzano
country: Italy
facility: Istituto Clinico Humanitas
city: Den Haag
country: Netherlands
facility: Haga ziekenhuis
city: Groningen
country: Netherlands
facility: UMCG
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Moscow
country: Russian Federation
facility: City Clinical Hospital # 40
city: Nizhny Novgorod
country: Russian Federation
facility: Nizhniy Novgorod Region Clinical Hospital
city: Saint-Petersburg
country: Russian Federation
facility: Saint Petersburg City Hospital #15
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp. Univ. de La Princesa
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: