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).
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
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
34
Talacotuzumab 9 mg/kg will be administered as an IV infusion.
Daratumumab 16 mg/kg will be administered as an IV infusion.
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
...and 11 more locations
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.
Time frame: Up to 2 years
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Up to 2 years
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