Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT04264806




Registration number
NCT04264806
Ethics application status
Date submitted
7/02/2020
Date registered
11/02/2020
Date last updated
20/05/2022

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
6/05/2021
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
28/01/2025
Actual
Sample size
Target
Accrual to date
Final
0
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
The purpose of the study is to compare overall response rate (ORR) between treatment groups
in participants with higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic
Leukemia (CMML) who are not eligible for Hematopoietic Stem Cell Transplantation (HSCT).
Trial website
https://clinicaltrials.gov/ct2/show/NCT04264806
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04264806