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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

URL:

https://clinicaltrials.gov/show/NCT03011034

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. The talacotuzumab arm of the study is closed for enrollment.

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. The talacotuzumab arm of the study is closed for enrollment.
  • 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:Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 8 Weeks
Time Frame:Up to 2 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 24 Weeks
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Time to Transfusion Independence (TI)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Duration of Transfusion Independence (TI)
Time Frame:Up to 2 years
Safety Issue:
Description:Duration of TI was reported. TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.
Measure:Percentage of Participants Who Met IWG Criteria for Transfusion Reduction
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Percentage of Participants With at Least One Dose of Myeloid Growth Factors Usage
Time Frame:Up to 2 years
Safety Issue:
Description:Percentage of participants with Myeloid Growth Factors (MGF) usage (who had used at least 1 dose of MGF) were reported.
Measure:Percentage of Participants With Hematologic Improvement (HI) Per IWG 2006 by Investigator Assessment
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Percentage of Participants With Complete Remission (CR) and Marrow CR
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Percentage of Participants With Partial Remission (PR)
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Percentage of Participants With Cytogenetic Response
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Overall Survival
Time Frame:Up to 2 years
Safety Issue:
Description: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.
Measure:Time to Progression to Acute Myeloid Leukemia (AML)
Time Frame:Up to 2 years
Safety Issue:
Description: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.

Details

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

Last Updated

June 11, 2021