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

NCT ID: NCT03011034

Last Updated: 2025-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-02-14
• Study Completion Date: 2021-10-05

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.

Conditions

Myelodysplastic Syndromes

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

Talacotuzumab

Intervention Type: DRUG

Talacotuzumab 9 mg/kg will be administered as an IV infusion.

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.

Group Type: EXPERIMENTAL

Daratumumab

Intervention Type: DRUG

Daratumumab 16 mg/kg will be administered as an IV infusion.

Interventions

Talacotuzumab

Talacotuzumab 9 mg/kg will be administered as an IV infusion.

Intervention Type: DRUG

Daratumumab

Daratumumab 16 mg/kg will be administered as an IV infusion.

Intervention Type: DRUG

Other Intervention Names

JNJ-56022473; JNJ-54767414

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

• Minimum Eligible Age: 18 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

Washington University School Of Medicine

St Louis, Missouri, United States

University of Pennsylvania Abramson Cancer Center

Philadelphia, Pennsylvania, United States

University of Texas, MD Anderson Cancer Center

Houston, Texas, United States

ZNA Stuivenberg

Antwerp, , Belgium

Az Groeninge

Kortrijk, , Belgium

UZ Leuven

Leuven, , Belgium

AZ Turnhout

Turnhout, , Belgium

Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna

Bologna, , Italy

Azienda Ospedaliero Universitaria Careggi

Florence, , Italy

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Pad. Marcora

Milan, , Italy

Istituto Clinico Humanitas

Rozzano, , Italy

UMCG

Groningen, , Netherlands

Erasmus MC

Rotterdam, , Netherlands

Haga ziekenhuis

The Hague, , Netherlands

City Clinical Hospital # 40

Moscow, , Russia

Nizhniy Novgorod Region Clinical Hospital

Nizhny Novgorod, , Russia

Saint Petersburg City Hospital #15

Saint Petersburg, , Russia

Hosp Univ Vall D Hebron

Barcelona, , Spain

Hosp. Univ. de La Princesa

Madrid, , Spain

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Hosp. Univ. I Politecni La Fe

Valencia, , Spain

Countries

United States; Belgium; Italy; Netherlands; Russia; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-003328-22

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

56022473MDS2002

Identifier Type: OTHER

Identifier Source: secondary_id

CR108261

Identifier Type: -

Identifier Source: org_study_id