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

Myelodysplastic Syndromes Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT03011034
• Other study ID #: CR108261
• Secondary ID: 2016-003328-2256
• Status: Completed
• Phase: Phase 2
• Start date: February 14, 2017
• Est. completion date: October 5, 2021

Study information

• Verified date: December 2022
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: October 5, 2021
• Est. primary completion date: January 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Talacotuzumab
Talacotuzumab 9 mg/kg will be administered as an IV infusion.
• Daratumumab
Daratumumab 16 mg/kg will be administered as an IV infusion.

Locations

Country	Name	City	State
Belgium	ZNA Stuivenberg	Antwerp
Belgium	Az Groeninge	Kortrijk
Belgium	UZ Leuven	Leuven
Belgium	AZ Turnhout	Turnhout
Italy	Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna	Bologna
Italy	Azienda Ospedaliero Universitaria Careggi	Firenze
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Pad. Marcora	Milano
Italy	Istituto Clinico Humanitas	Rozzano
Netherlands	Haga ziekenhuis	Den Haag
Netherlands	UMCG	Groningen
Netherlands	Erasmus MC	Rotterdam
Russian Federation	City Clinical Hospital # 40	Moscow
Russian Federation	Nizhniy Novgorod Region Clinical Hospital	Nizhny Novgorod
Russian Federation	Saint Petersburg City Hospital #15	Saint-Petersburg
Spain	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
United States	University of Texas, MD Anderson Cancer Center	Houston	Texas
United States	University of Pennsylvania-Abramson Cancer Center	Philadelphia	Pennsylvania
United States	Washington University School of Medicine	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Belgium,  Italy,  Netherlands,  Russian Federation,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years