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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04264806




Registration number
NCT04264806
Ethics application status
Date submitted
7/02/2020
Date registered
11/02/2020

Titles & IDs
Public title
A Study of Cusatuzumab in Combination With Azacitidine Compared With Azacitidine Alone in Patients With Higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Who Are Not Candidates for Hematopoietic Stem Cell Transplantation (HSCT)
Scientific title
A Phase 2, Randomized, Open-label Study of Cusatuzumab in Combination With Azacitidine Compared With Azacitidine Alone in Patients With Higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Who Are Not Candidates for Hematopoietic Stem Cell Transplantation (HSCT)
Secondary ID [1] 0 0
2019-003576-40
Secondary ID [2] 0 0
CR108734
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 0 0
Leukemia, Myelomonocytic, Chronic 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Azacitidine
Treatment: Drugs - Cusatuzumab

Experimental: Azacitidine: Participants with MDS or CMML - Participants with higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) will receive azacitidine 75 milligram per meter square (mg/m\^2) body surface area (BSA) subcutaneously or Intravenously per local label on Days 1 through Day 7 of each 28-day cycle. Participants will be treated until disease progression; relapse from complete remission (CR), partial remission (PR), or marrow complete remission (mCR); transformation to acute myeloid leukemia (AML); death; or unacceptable toxicity.

Experimental: Azacitidine and Cusatuzumab: Participants with MDS or CMML - Participants with higher-risk MDS or CMML will receive azacitidine 75 mg/m\^2 BSA subcutaneously or Intravenously per local label on Days 1 through 7 and cusatuzumab 20 mg/kg IV on Days 3 and 17 of each 28-day cycle. Participants will be treated until disease progression; relapse from CR, PR, mCR; transformation to AML; death; or unacceptable toxicity.


Treatment: Drugs: Azacitidine
Participants will receive subcutaneous (SC) or intravenous (IV) injection of Azacitidine 75 mg/m\^2.

Treatment: Drugs: Cusatuzumab
Participants will receive SC or IV injection of Cusatuzumab 20 mg/kg.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Overall Response Rate (ORR)
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [1] 0 0
Percentage of Participants Achieving Complete Remission (CR)
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [2] 0 0
Percentage of Participants who Achieve Transfusion Independence
Timepoint [2] 0 0
Up to 4 years
Secondary outcome [3] 0 0
Time to Transformation of Participants to Acute Myeloid Leukemia (AML)
Timepoint [3] 0 0
Up to 4 years
Secondary outcome [4] 0 0
Progression Free Survival (PFS)
Timepoint [4] 0 0
Up to 4 years
Secondary outcome [5] 0 0
Overall Survival (OS)
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Hematologic Improvement Rate
Timepoint [6] 0 0
Up to 4 years
Secondary outcome [7] 0 0
Percentage of Participants With Adverse Events (AEs) as a Measure of Safety and Tolerability
Timepoint [7] 0 0
Up to 4 years
Secondary outcome [8] 0 0
Percentage of Participants With Clinically Significant Abnormalities in Laboratory Parameters
Timepoint [8] 0 0
Up to 4 years
Secondary outcome [9] 0 0
Area Under the Serum Concentration-Time Curve Within Timespan t1 to t2 (AUC[t1-t2]) of Cusatuzumab
Timepoint [9] 0 0
Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Secondary outcome [10] 0 0
Maximum Serum Concentration (Cmax) of Cusatuzumab
Timepoint [10] 0 0
Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Secondary outcome [11] 0 0
Minimum Serum Concentration (Cmin) of Cusatuzumab
Timepoint [11] 0 0
Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Secondary outcome [12] 0 0
Elimination Half-Life (t1/2) of Cusatuzumab
Timepoint [12] 0 0
Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Secondary outcome [13] 0 0
Systemic Clearance (CL) of Cusatuzumab
Timepoint [13] 0 0
Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Secondary outcome [14] 0 0
Volume of Distribution (Vz) of Cusatuzumab
Timepoint [14] 0 0
Cycle 1: Day 3,17 (predose, end of infusion [EOI] postdose), Day 4 (24 hours postdose) Cycle 2, 3, 4, 8, 11: Day 3 (predose, EOI postdose); Cycle 4 Day 21 to Cycle 5: Day 1(at disease evaluation); and end of treatment (EOT) [up to 4 years])
Secondary outcome [15] 0 0
Number of Participants with Developed Antidrug Antibodies to Cusatuzumab
Timepoint [15] 0 0
Cycle 1: Day 3 (Predose); Cycle 1: Day 17 (Predose); Cycle 2: Day 3 (Predose); Cycle 8 and 11: Day 3 (Predose) and EOT (up to 4 years)
Secondary outcome [16] 0 0
Percentage of Participants Achieving Complete Remission (CR) and Partial Remission (PR)
Timepoint [16] 0 0
Up to 4 years
Secondary outcome [17] 0 0
Time to response
Timepoint [17] 0 0
Up to 4 years
Secondary outcome [18] 0 0
Duration of response
Timepoint [18] 0 0
Up to 4 years
Secondary outcome [19] 0 0
Percentage of Participants With Clinically Meaningful Improvement in Functional Assessment of Cancer Therapy - Anemia Trial Outcome Index (FACT-An TOI) Total Score
Timepoint [19] 0 0
Up to 4 years

Eligibility
Key inclusion criteria
* Diagnosis of de novo or secondary higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) per World Health Organization (WHO) 2016 criteria
* At study entry, higher-risk MDS (intermediate, high, and very high risk MDS per Revised International Prognostic Scoring System [IPSS R]) OR higher-risk CMML (intermediate-2 or high risk CMML per CMML-specific Prognostic Scoring System [CPSS-Mol]). Participants with previous lower-risk MDS or CMML that has evolved to higher-risk MDS or CMML are eligible
* At study entry, not a candidate for Hematopoietic Stem Cell Transplantation (HSCT)
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
* Adequate liver and renal function defined as follows: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less than (<) 3 * upper limit of normal (ULN); Total bilirubin less than or equal to (<=) 1.5 * ULN, unless bilirubin rise is due to Gilbert's syndrome or of non hepatic origin; and Creatinine clearance (CrCl) greater than (>) 30 milliliter per minute per 1.73 square meters (mL/min/1.73 m^2) (by Modification of Diet in Renal Disease formula)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Received prior HSCT or any prior treatment, including hypomethylating agent (HMAs), for higher-risk MDS or CMML. Prior supportive therapies including transfusion and growth factors are acceptable
* Received prior treatment with cusatuzumab
* Presence of the breakpoint cluster region protein-Abelson murine leukemia (bcr-abl) rearrangement
* Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug
* Any active systemic infection

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
St Vincents Hospital Sydney - Darlinghurst
Recruitment hospital [2] 0 0
St Vincents Hospital Melbourne - Fitzroy
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Institute - Melbourne
Recruitment hospital [4] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [5] 0 0
Westmead Hospital - Westmead
Recruitment hospital [6] 0 0
Wollongong Hospital - Wollongong
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
3065 - Fitzroy
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
6000 - Perth
Recruitment postcode(s) [5] 0 0
2145 - Westmead
Recruitment postcode(s) [6] 0 0
2500 - Wollongong
Recruitment outside Australia
Country [1] 0 0
Brazil
State/province [1] 0 0
Curitiba
Country [2] 0 0
Brazil
State/province [2] 0 0
Florianopolis
Country [3] 0 0
Brazil
State/province [3] 0 0
Natal
Country [4] 0 0
Brazil
State/province [4] 0 0
Porto Alegre
Country [5] 0 0
Brazil
State/province [5] 0 0
Rio De Janeiro
Country [6] 0 0
Brazil
State/province [6] 0 0
São José do Rio Preto
Country [7] 0 0
Brazil
State/province [7] 0 0
São Paulo
Country [8] 0 0
France
State/province [8] 0 0
Angers
Country [9] 0 0
France
State/province [9] 0 0
Lille
Country [10] 0 0
France
State/province [10] 0 0
Limoges
Country [11] 0 0
France
State/province [11] 0 0
Marseille
Country [12] 0 0
France
State/province [12] 0 0
Nice
Country [13] 0 0
France
State/province [13] 0 0
Paris Cedex 10
Country [14] 0 0
France
State/province [14] 0 0
Paris, 75
Country [15] 0 0
France
State/province [15] 0 0
Tours
Country [16] 0 0
France
State/province [16] 0 0
Vandoeuvre Les Nancy
Country [17] 0 0
Germany
State/province [17] 0 0
Dresden
Country [18] 0 0
Germany
State/province [18] 0 0
Freiburg Im Breisgau
Country [19] 0 0
Germany
State/province [19] 0 0
Hannover
Country [20] 0 0
Germany
State/province [20] 0 0
Leipzig
Country [21] 0 0
Germany
State/province [21] 0 0
München
Country [22] 0 0
Germany
State/province [22] 0 0
Ulm
Country [23] 0 0
Italy
State/province [23] 0 0
Bologna
Country [24] 0 0
Italy
State/province [24] 0 0
Cona
Country [25] 0 0
Italy
State/province [25] 0 0
Novara
Country [26] 0 0
Italy
State/province [26] 0 0
Orbassano
Country [27] 0 0
Italy
State/province [27] 0 0
Reggio Calabria
Country [28] 0 0
Italy
State/province [28] 0 0
Roma
Country [29] 0 0
Italy
State/province [29] 0 0
Rozzano
Country [30] 0 0
Russian Federation
State/province [30] 0 0
Dzerzhinsk
Country [31] 0 0
Russian Federation
State/province [31] 0 0
Moscow
Country [32] 0 0
Russian Federation
State/province [32] 0 0
Nizhny Novgorod
Country [33] 0 0
Russian Federation
State/province [33] 0 0
Ryazan
Country [34] 0 0
Russian Federation
State/province [34] 0 0
Saint-Petersburg
Country [35] 0 0
Russian Federation
State/province [35] 0 0
St-Petersburg
Country [36] 0 0
Russian Federation
State/province [36] 0 0
St. Petersburg
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Syktyvkar
Country [38] 0 0
Saudi Arabia
State/province [38] 0 0
Dammam
Country [39] 0 0
Saudi Arabia
State/province [39] 0 0
Jeddah
Country [40] 0 0
Saudi Arabia
State/province [40] 0 0
Riyadh
Country [41] 0 0
Spain
State/province [41] 0 0
Badalona
Country [42] 0 0
Spain
State/province [42] 0 0
Barcelona
Country [43] 0 0
Spain
State/province [43] 0 0
Madrid
Country [44] 0 0
Spain
State/province [44] 0 0
Palma
Country [45] 0 0
Spain
State/province [45] 0 0
Salamanca
Country [46] 0 0
Spain
State/province [46] 0 0
Sevilla
Country [47] 0 0
Switzerland
State/province [47] 0 0
Bern
Country [48] 0 0
Switzerland
State/province [48] 0 0
Geneve
Country [49] 0 0
Switzerland
State/province [49] 0 0
Zürich
Country [50] 0 0
Turkey
State/province [50] 0 0
Ankara
Country [51] 0 0
Turkey
State/province [51] 0 0
Istanbul
Country [52] 0 0
Turkey
State/province [52] 0 0
Izmir
Country [53] 0 0
Turkey
State/province [53] 0 0
Samsun
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Leeds
Country [55] 0 0
United Kingdom
State/province [55] 0 0
London
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Newcastle Upun Tyne
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Oxford

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Janssen Research & Development, LLC
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
argenx
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Janssen Research & Development, LLC Clinical trials
Address 0 0
Janssen Research & Development, LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson \& Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.janssen.com/clinical-trials/transparency


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.