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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

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ClinicalTrials.gov Identifier: NCT03011034
Recruitment Status : Completed
First Posted : January 5, 2017
Results First Posted : March 13, 2020
Last Update Posted : December 30, 2022
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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).

Condition or disease Intervention/treatment Phase
Myelodysplastic Syndromes Drug: Talacotuzumab Drug: Daratumumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: 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
Actual Study Start Date : February 14, 2017
Actual Primary Completion Date : January 23, 2019
Actual Study Completion Date : October 5, 2021


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 Name: 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 Name: JNJ-54767414




Primary Outcome Measures :
  1. Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 8 Weeks [ Time Frame: Up to 2 years ]
    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 :
  1. Percentage of Participants Who Achieved Red Blood Cell (RBC) Transfusion Independence (TI) Lasting at Least 24 Weeks [ Time Frame: Up to 2 years ]
    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.

  2. Time to Transfusion Independence (TI) [ Time Frame: Up to 2 years ]
    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.

  3. Duration of Transfusion Independence (TI) [ Time Frame: Up to 2 years ]
    Duration of TI was reported. TI was defined as absence of RBC transfusion during any consecutive 56 days (8 weeks) post randomization.

  4. Percentage of Participants Who Met IWG Criteria for Transfusion Reduction [ Time Frame: Up to 2 years ]
    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.

  5. Percentage of Participants With at Least One Dose of Myeloid Growth Factors Usage [ Time Frame: Up to 2 years ]
    Percentage of participants with Myeloid Growth Factors (MGF) usage (who had used at least 1 dose of MGF) were reported.

  6. Percentage of Participants With Hematologic Improvement (HI) Per IWG 2006 by Investigator Assessment [ Time Frame: Up to 2 years ]
    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.

  7. Percentage of Participants With Complete Remission (CR) and Marrow CR [ Time Frame: Up to 2 years ]
    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.

  8. Percentage of Participants With Partial Remission (PR) [ Time Frame: Up to 2 years ]
    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.

  9. Percentage of Participants With Cytogenetic Response [ Time Frame: Up to 2 years ]
    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.

  10. Overall Survival [ Time Frame: Up to 2 years ]
    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.

  11. Time to Progression to Acute Myeloid Leukemia (AML) [ Time Frame: Up to 2 years ]

    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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03011034


Locations
Show Show 21 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
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Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
  Study Documents (Full-Text)

Documents provided by Janssen Research & Development, LLC:
Study Protocol  [PDF] December 13, 2018
Statistical Analysis Plan  [PDF] September 21, 2018

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Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT03011034    
Other Study ID Numbers: CR108261
2016-003328-22 ( EudraCT Number )
56022473MDS2002 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: January 5, 2017    Key Record Dates
Results First Posted: March 13, 2020
Last Update Posted: December 30, 2022
Last Verified: December 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Preleukemia
Myelodysplastic Syndromes
Syndrome
Disease
Pathologic Processes
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Daratumumab
Antineoplastic Agents