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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

NCT03011034

Description:

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).

Related Conditions:
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: CR108261
  • SECONDARY ID: 2016-003328-22
  • SECONDARY ID: 56022473MDS2002
  • NCT ID: NCT03011034

Conditions

  • Myelodysplastic Syndromes

Interventions

DrugSynonymsArms
TalacotuzumabJNJ-56022473Talacotuzumab
DaratumumabJNJ-54767414Daratumumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
TalacotuzumabExperimentalParticipants 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.
  • Talacotuzumab
    DaratumumabExperimentalParticipants 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.
      • Daratumumab

    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

    Maximum Eligible Age:N/A
    Minimum Eligible Age:18 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Red Blood Cell (RBC) Transfusion Independence (TI) for 8 Weeks
    Time Frame:Up to 2 years
    Safety Issue:
    Description:RBC TI is defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.

    Secondary Outcome Measures

    Measure:Number of Participants With Transfusion Independence Lasting 168 days (24 weeks)
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Time to Transfusion Independence (TI)
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Duration of Transfusion Independence (TI)
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Number of Participants who Received Transfusions
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Number of Participants With Myeloid Growth Factors Usage
    Time Frame:Up to 2 years
    Safety Issue:
    Description:
    Measure:Number of Participants With Hematologic Improvement - Erythroid (HI-E) Response
    Time Frame:Up to 2 years
    Safety Issue:
    Description:International Working Group (IWG) Response Criteria 2006 for Hematologic Improvement - Erythroid response: hemoglobin (Hb) increase by greater than or equal to (>=)1.5 gram per deciliter (g/dL) and 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.
    Measure:Number of Participants With Hematologic Improvement - Platelet (HI-P) Response
    Time Frame:Up to 2 years
    Safety Issue:
    Description:IWG Response Criteria 2006 for Hematologic Improvement- Platelet response: absolute increase of >=30*109/Liter (L) for participants starting with greater than (>)20*109/L platelets and increase from <20*109/L to >20*109/L and by at least 100 percent (%).
    Measure:Number of Participants With Hematologic Improvement - Neutrophil (HI-N) Response
    Time Frame:Up to 2 years
    Safety Issue:
    Description:IWG Response Criteria 2006 for Hematologic Improvement- Neutrophil response: at least 100% increase and an absolute increase >0.5*109/L.
    Measure:Complete Remission (CR)
    Time Frame:Up to 2 years
    Safety Issue:
    Description:IWG Response Criteria 2006 for Complete remission: Bone marrow- less than or equal to (<=)5 percent (%) myeloblasts with normal maturation of all cell lines and peripheral blood: Hemoglobin (Hb) >=11 g/dL; platelets >=100*10^9/L; neutrophils >=1.0*10^9/L; blasts, 0%.
    Measure:Partial Remission (PR)
    Time Frame:Up to 2 years
    Safety Issue:
    Description:IWG Response Criteria 2006 for Partial remission: All CR criteria if abnormal before treatment except: bone marrow blasts decreased by >=50% over pretreatment but still >5%.
    Measure:Cytogenetic Response
    Time Frame:Up to 2 years
    Safety Issue:
    Description:IWG Response Criteria 2006 for Cytogenetic response: Complete- disappearance of the chromosomal abnormality without appearance of new ones. Partial- At least 50% reduction of the chromosomal abnormality.
    Measure:Overall Survival (OS)
    Time Frame:Up to 2 years
    Safety Issue:
    Description:Overall survival was defined as the interval between the date of randomization and the date of death from any cause.
    Measure:Progression to Acute Myeloid Leukemia (AML)
    Time Frame:Up to 2 years
    Safety Issue:
    Description:

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Janssen Research & Development, LLC

    Trial Keywords

      Last Updated

      February 2, 2017