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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04264806
Ethics application status
Date submitted
7/02/2020
Date registered
11/02/2020
Date last updated
29/10/2020

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) - ORR is a composite of complete remission (CR), partial remission (PR) and marrow complete remission (mCR) as per modified International Working Group (IWG) criteria.
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [1] 0 0
Percentage of Participants Achieving Complete Remission (CR) - Percentage of participants achieving CR as per IWG criteria will be reported.
Timepoint [1] 0 0
Up to 4 years
Secondary outcome [2] 0 0
Percentage of Participants who Achieve Transfusion Independence - Percentage of participants who achieve transfusion independence will be reported. Transfusion independence is defined as a period of greater than or equal to (>=) 56 consecutive days with no transfusion occurring between the first and last dose of study drug +30 days.
Timepoint [2] 0 0
Up to 4 years
Secondary outcome [3] 0 0
Time to Transformation of Participants to Acute Myeloid Leukemia (AML) - Time to transformation of participants to AML will be reported. Transformation to AML is defined as >= 20% bone marrow blasts.
Timepoint [3] 0 0
Up to 4 years
Secondary outcome [4] 0 0
Progression Free Survival (PFS) - PFS is defined as the time from randomization to disease progression; relapse from CR, PR, or mCR; or death from any cause.
Timepoint [4] 0 0
Up to 4 years
Secondary outcome [5] 0 0
Overall Survival (OS) - OS is defined as the time from randomization to death.
Timepoint [5] 0 0
Up to 4 years
Secondary outcome [6] 0 0
Hematologic Improvement Rate - Hematologic improvement rate is defined as erythroid response (pretreatment, less than (<) 11 g/dL; hemoglobin >= 1.5 g/dL; relevant reduction of units of RBC transfusions by an absolute number of >= 4 Red blood cell (RBC) transfusions/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks. Only RBC transfusions given for a hemoglobin of <= 9.0 g/dL pretreatment will count in the RBC transfusion response evaluation; platelet response (pretreatment <100*10^9/L); absolute increase of >= 30*109/L for participants starting with >20*10^9/L platelets; increase to >20*109/L and by >= 100% for participants starting with <= 20*109/L platelets; Neutrophil response (pretreatment <1.0×10^9/L); and at least 100% increase and an absolute increase of >0.5*10^9/L.
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 - An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.
Timepoint [7] 0 0
Up to 4 years
Secondary outcome [8] 0 0
Percentage of Participants With Clinically Significant Abnormalities in Laboratory Parameters - Percentage of participants with clinically significant abnormalities in laboratory parameters will be reported.
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 - The AUC(t1-t2) is the area under the serum concentration-time curve within timespan t1 to t2.
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 - Cmax is the maximum observed serum concentration.
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 - Cmin is the minimum observed serum concentration.
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 - T1/2 is the time measured for the serum concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
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 - CL is a quantitative measure of the rate at which a drug substance is removed from the body.
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 - The Vz is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug.
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 - Venous blood samples are analyzed for presence of antidrug antibodies to cusatuzumab. Participants with titer of confirmed positive samples for cusatuzumab antibodies are reported.
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) - Percentage of participants achieving CR and PR as per IWG criteria will be reported.
Timepoint [16] 0 0
Up to 4 years
Secondary outcome [17] 0 0
Time to response - Time to response for participants who achieved CR, PR and mCR responses, defined as time from randomization to achieving the first response of CR, PR, or mCR as per modified IWG criteria.
Timepoint [17] 0 0
Up to 4 years
Secondary outcome [18] 0 0
Duration of response - Time from achieving the first response of CR, PR, or mCR to relapse or death from any cause for those participants who responded.
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 - FACT-An is a scale in Functional Assessment of Chronic Illness Therapy Measurement System. It consists of Functional Assessment of Cancer Therapy (general version; FACT-G) and 20 questions labeled "additional concerns" that measure anemia/fatigue. FACT-G is 27-item compilation of general questions divided into 4 primary quality of life domains: physical well-being, social/family well-being, emotional wellbeing, and functional well-being. Participants will be asked to rate scale items as it applies to past 7 days, on 5-point scale (0=Not at all, 1=A little bit, 2=Somewhat, 3=Quite a bit, 4=Very much). Negatively stated items will be reversed by subtracting the response from 4. After reversing the proper items, items are summed to a total to generate a score on (sub)scale. A summary Trial Outcome Index total score (FACT An TOI) will be calculated by summing physical well being, functional well being, and anemia symptoms subscales and higher is the score better is the quality of life.
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
Gender
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
Not yet recruiting
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
Gold Coast University Hospital - Gold Coast
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Institute - Melbourne
Recruitment hospital [5] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [6] 0 0
Westmead Hospital - Westmead
Recruitment hospital [7] 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
4215 - Gold Coast
Recruitment postcode(s) [4] 0 0
- Melbourne
Recruitment postcode(s) [5] 0 0
6000 - Perth
Recruitment postcode(s) [6] 0 0
2145 - Westmead
Recruitment postcode(s) [7] 0 0
2500 - Wollongong
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
Louisiana
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Oregon
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
United States of America
State/province [10] 0 0
Vermont
Country [11] 0 0
United States of America
State/province [11] 0 0
Wisconsin
Country [12] 0 0
Brazil
State/province [12] 0 0
Curitiba
Country [13] 0 0
Brazil
State/province [13] 0 0
Florianopolis
Country [14] 0 0
Brazil
State/province [14] 0 0
Natal
Country [15] 0 0
Brazil
State/province [15] 0 0
Porto Alegre
Country [16] 0 0
Brazil
State/province [16] 0 0
Rio De Janeiro
Country [17] 0 0
Brazil
State/province [17] 0 0
São José do Rio Preto
Country [18] 0 0
Brazil
State/province [18] 0 0
São Paulo
Country [19] 0 0
France
State/province [19] 0 0
Angers
Country [20] 0 0
France
State/province [20] 0 0
Lille
Country [21] 0 0
France
State/province [21] 0 0
Limoges
Country [22] 0 0
France
State/province [22] 0 0
Marseille
Country [23] 0 0
France
State/province [23] 0 0
Nice
Country [24] 0 0
France
State/province [24] 0 0
Paris Cedex 10
Country [25] 0 0
France
State/province [25] 0 0
Paris, 75
Country [26] 0 0
France
State/province [26] 0 0
Tours
Country [27] 0 0
France
State/province [27] 0 0
Vandoeuvre Les Nancy
Country [28] 0 0
Germany
State/province [28] 0 0
Dresden
Country [29] 0 0
Germany
State/province [29] 0 0
Freiburg Im Breisgau
Country [30] 0 0
Germany
State/province [30] 0 0
Hannover
Country [31] 0 0
Germany
State/province [31] 0 0
Leipzig
Country [32] 0 0
Germany
State/province [32] 0 0
München
Country [33] 0 0
Germany
State/province [33] 0 0
Ulm
Country [34] 0 0
Italy
State/province [34] 0 0
Bologna
Country [35] 0 0
Italy
State/province [35] 0 0
Cona
Country [36] 0 0
Italy
State/province [36] 0 0
Novara
Country [37] 0 0
Italy
State/province [37] 0 0
Orbassano
Country [38] 0 0
Italy
State/province [38] 0 0
Reggio Calabria
Country [39] 0 0
Italy
State/province [39] 0 0
Roma
Country [40] 0 0
Italy
State/province [40] 0 0
Rozzano
Country [41] 0 0
Russian Federation
State/province [41] 0 0
Dzerzhinsk
Country [42] 0 0
Russian Federation
State/province [42] 0 0
Moscow
Country [43] 0 0
Russian Federation
State/province [43] 0 0
Nizhny Novgorod
Country [44] 0 0
Russian Federation
State/province [44] 0 0
Ryazan
Country [45] 0 0
Russian Federation
State/province [45] 0 0
Saint-Petersburg
Country [46] 0 0
Russian Federation
State/province [46] 0 0
St-Petersburg
Country [47] 0 0
Russian Federation
State/province [47] 0 0
St. Petersburg
Country [48] 0 0
Russian Federation
State/province [48] 0 0
Syktyvkar
Country [49] 0 0
Saudi Arabia
State/province [49] 0 0
Dammam
Country [50] 0 0
Saudi Arabia
State/province [50] 0 0
Jeddah
Country [51] 0 0
Saudi Arabia
State/province [51] 0 0
Riyadh
Country [52] 0 0
Spain
State/province [52] 0 0
Badalona
Country [53] 0 0
Spain
State/province [53] 0 0
Barcelona
Country [54] 0 0
Spain
State/province [54] 0 0
Madrid
Country [55] 0 0
Spain
State/province [55] 0 0
Palma
Country [56] 0 0
Spain
State/province [56] 0 0
Salamanca
Country [57] 0 0
Spain
State/province [57] 0 0
Sevilla
Country [58] 0 0
Switzerland
State/province [58] 0 0
Bern
Country [59] 0 0
Switzerland
State/province [59] 0 0
Geneve
Country [60] 0 0
Switzerland
State/province [60] 0 0
Zürich
Country [61] 0 0
Turkey
State/province [61] 0 0
Ankara
Country [62] 0 0
Turkey
State/province [62] 0 0
Istanbul
Country [63] 0 0
Turkey
State/province [63] 0 0
Izmir
Country [64] 0 0
Turkey
State/province [64] 0 0
Samsun
Country [65] 0 0
United Kingdom
State/province [65] 0 0
Leeds
Country [66] 0 0
United Kingdom
State/province [66] 0 0
London
Country [67] 0 0
United Kingdom
State/province [67] 0 0
Newcastle Upun Tyne
Country [68] 0 0
United Kingdom
State/province [68] 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/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
Study Contact
Address 0 0
Country 0 0
Phone 0 0
844-434-4210
Fax 0 0
Email 0 0
JNJ.CT@sylogent.com
Contact person for scientific queries

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