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

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

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).

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Talacotuzumab; Drug: Daratumumab

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.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Antwerp, Belgium, 2060
    • ZNA Stuivenberg
  • Kortrijk, Belgium, 8500
    • AZ Groeninge
  • Leuven, Belgium, 3000
    • UZ Leuven
  • Turnhout, Belgium, 2300
    • Az Turnhout
• Italy
  • Bologna, Italy, 40138
    • Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
  • Firenze, Italy, 50134
    • Azienda Ospedaliero Universitaria Careggi
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Pad. Marcora
  • Rozzano, Italy, 20089
    • Istituto Clinico Humanitas
• Netherlands
  • Den Haag, Netherlands, 2545 CH
    • Haga Ziekenhuis
  • Groningen, Netherlands, 9713 GZ
    • UMCG
  • Rotterdam, Netherlands, 3075 EA
    • Erasmus MC
• Russian Federation
  • Moscow, Russian Federation, 129301
    • City Clinical Hospital # 40
  • Nizhny Novgorod, Russian Federation, 603126
    • Nizhniy Novgorod Region Clinical Hospital
  • Saint-Petersburg, Russian Federation, 123182
    • Saint Petersburg City Hospital #15
• Spain
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Madrid, Spain, 28006
    • Hosp. Univ. de La Princesa
  • Salamanca, Spain, 37007
    • Hosp Clinico Univ de Salamanca
  • Valencia, Spain, 46026
    • Hosp. Univ. I Politecni La Fe
• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Abramson Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas, MD Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

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: Talacotuzumab; Participants will receive talacotuzumab 9 milligram per kilogram (mg/kg) intravenously (IV) on Days 1 and 15 for all cycles. Each treatment cycle is of 28 days. The talacotuzumab arm of the study is closed for enrollment.	Drug: Talacotuzumab; Talacotuzumab 9 mg/kg will be administered as an IV infusion.; Other Names: JNJ-56022473
Experimental: Daratumumab; Participants will receive daratumumab 16 mg/kg IV on Days 1, 8, 15, and 22 for Cycles 1 and 2; on Days 1 and 15 for Cycles 3 to 6; and on Day 1 for all subsequent cycles. Each treatment cycle is of 28 days.	Drug: Daratumumab; Daratumumab 16 mg/kg will be administered as an IV infusion.; Other Names: JNJ-54767414

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 8 Weeks	Percentage of participants who achieved RBC TI lasting at least 8 weeks were reported. RBC TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 24 Weeks	Percentage of participants who achieved RBC TI lasting at least 24 weeks were reported. RBC TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.	Up to 2 years
Time to Transfusion Independence (TI)	Time to transfusion independence (TI) was defined as time to the start of the TI interval. TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.	Up to 2 years
Duration of Transfusion Independence (TI)	Duration of TI was reported. TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.	Up to 2 years
Percentage of Participants Who Met IWG Criteria for Transfusion Reduction	Percentage of participants who met IWG criteria for transfusion reduction were reported. IWG criteria for transfusion reduction: at least 4 units reduction in RBC transfusions in the best 8-week interval. The best 8-week interval was a post-baseline 8-week interval where the participant had the fewest post-baseline RBC transfusion units.	Up to 2 years
Percentage of Participants With at Least One Dose of Myeloid Growth Factors Usage	Percentage of participants with Myeloid Growth Factors (MGF) usage (who had used at least 1 dose of MGF) were reported.	Up to 2 years
Percentage of Participants With Hematologic Improvement (HI) Per IWG 2006 by Investigator Assessment	Percentage of participants with HI per International Working Group (IWG) 2006 by investigator assessment were reported. Response criteria per IWG 2006 for HI: Erythroid response (pretreatment, less than [<]11 gram per deciliter [g/dL]) - hemoglobin increase by greater than or equal to (>=)1.5 g/dL, relevant reduction of units of RBC transfusions by an absolute number of at least 4 RBC transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a Hb of <=9 g/dL pretreatment counted in the RBC transfusion response evaluation; Platelet response (pretreatment, <100*10^9/L) - absolute increase of >=30*10^9/L for participants starting with >20*10^9/L platelets. Increase from <20*10^9/L to >20*10^9/L and by at least 100 percent (%); Neutrophil response (pretreatment, <1*10^9/L) - at least 100% increase and an absolute increase >0.5*10^9/L.	Up to 2 years
Percentage of Participants With Complete Remission (CR) and Marrow CR	Percentage of participants with CR and marrow CR were reported. CR per International Working Group (IWG) 2006 Response criteria: Bone marrow - less than or equal to (<=)5% myeloblasts with normal maturation of all cell lines, persistent dysplasia noted; Peripheral blood - hemoglobin >=11 g/dL; platelets >=100*10^9/L; neutrophils >=1.0*10^9/L; blasts, 0%. Marrow CR: Bone marrow - <=5% myeloblasts and decrease by >=50% over pretreatment; Peripheral blood - if HI responses, they were noted in addition to marrow CR.	Up to 2 years
Percentage of Participants With Partial Remission (PR)	Percentage of participants with PR were reported. PR per International Working Group (IWG) 2006 Response criteria: All CR criteria if abnormal before treatment except: Bone marrow blasts decreased by >=50% over pretreatment but still >5%, cellularity and morphology not relevant.	Up to 2 years
Percentage of Participants With Cytogenetic Response	Percentage of participants with cytogenetic response were reported. Cytogenetic response per International Working Group (IWG) 2006 Response criteria: Complete - disappearance of the chromosomal abnormality without appearance of new ones; Partial - at least 50% reduction of the chromosomal abnormality.	Up to 2 years
Overall Survival	The overall survival was defined as the time from the date of first dose of study drug to date of death from any cause. Median overall survival was estimated by using the Kaplan-Meier method.	Up to 2 years
Time to Progression to Acute Myeloid Leukemia (AML)	Time to progression to acute myeloid leukemia was reported. Disease progression as per IWG response criteria: For participants with: <5% blasts: >=50% increase in blasts to >5% blasts; 5%-10% blasts: >=50% increase to >10% blasts; 10%-20% blasts: >=50% increase to >20% blasts; 20%-30% blasts: >=50% increase to >30% blasts. Any of the following: >=50% decrement from maximum remission/response in granulocytes or platelets; reduction in hemoglobin by >=2 g/dL; transfusion dependence.	Up to 2 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2017
• Primary Completion (Actual): January 23, 2019
• Study Completion (Actual): October 5, 2021

Study Registration Dates

• First Submitted: January 4, 2017
• First Submitted That Met QC Criteria: January 4, 2017
• First Posted (Estimated): January 5, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 3, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Hematologic Diseases; Precancerous Conditions; Bone Marrow Diseases; Syndrome; Preleukemia; Myelodysplastic Syndromes; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: CR108261; 2016-003328-22 (EudraCT Number); 56022473MDS2002 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

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