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    Summary
    EudraCT Number:2019-003576-40
    Sponsor's Protocol Code Number:74494550MDS2001
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2020-02-06
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2019-003576-40
    A.3Full title of the trial
    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)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Clinical 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)
    A.4.1Sponsor's protocol code number74494550MDS2001
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorJanssen-Cilag International N.V.
    B.1.3.4CountryBelgium
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportJanssen Research & Development, LLC
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationJanssen-Cilag International N.V.
    B.5.2Functional name of contact pointClinical Registry Group
    B.5.3 Address:
    B.5.3.1Street AddressArchimedesweg 29
    B.5.3.2Town/ cityLeiden
    B.5.3.3Post code2333
    B.5.3.4CountryNetherlands
    B.5.4Telephone number+31715242166
    B.5.5Fax number+31715242110
    B.5.6E-mailClinicalTrialsEU@its.jnj.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCusatuzumab
    D.3.2Product code JNJ-74494550
    D.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCUSATUZUMAB
    D.3.9.1CAS number 1864871-20-4
    D.3.9.2Current sponsor codeJNJ-74494550
    D.3.9.4EV Substance CodeSUB195527
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)
    E.1.1.1Medical condition in easily understood language
    Blood Cancer
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10028533
    E.1.2Term Myelodysplastic syndrome
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.0
    E.1.2Level LLT
    E.1.2Classification code 10054350
    E.1.2Term Chronic myelomonocytic leukemia
    E.1.2System Organ Class 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To compare overall response rate (ORR) between treatment groups in subjects with higher-risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) who are not eligible for hematopoietic stem cell transplantation (HSCT)
    E.2.2Secondary objectives of the trial
    1. To compare the following between treatment groups:
    • Proportion of subjects achieving complete remission (CR)+partial remission (PR)
    • Proportion of subjects achieving CR
    • Time to response
    • Duration of response
    • Transfusion (red blood cell [RBC] or platelets) independence
    • Transformation to acute myeloid leukemia (AML) according to World Health Organization (WHO) criteria
    • Progression-free survival (PFS)
    • Overall survival (OS)
    • Hematologic improvement
    2. To assess the safety profile of cusatuzumab in combination with azacitidine
    3. To assess changes in physical function/symptoms
    4. To assess the pharmacokinetics (PK) of cusatuzumab in combination with azacitidine
    5. To assess the immunogenicity of cusatuzumab
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Each potential subject must satisfy all of the following criteria to be randomized in the study:
    1. Age ≥18 years.
    2. Diagnosis of de novo or secondary higher-risk MDS or CMML per WHO 2016 criteria.
    3. At study entry, higher-risk MDS (intermediate, high, and very high risk MDS per IPSS-R) OR higher-risk CMML (intermediate-2 or high risk CMML per CPSS-Mol). Appendix 5 of the protocol presents the relevant prognostic tools. Subjects with previous lower-risk MDS or CMML that has evolved to higher-risk MDS or CMML are eligible.
    4. At study entry, not a candidate for HSCT.
    5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
    6. Adequate liver and renal function defined as follows:
    • Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) <3× upper limit of normal (ULN)
    • Total bilirubin ≤1.5×ULN, unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin
    • Creatinine clearance (CrCl) >30 mL/min/1.73 m² (by Modification of Diet in Renal Disease formula).
    7. A woman of childbearing potential must have a negative highly-sensitive serum (β-human chorionic gonadotropin [β-hCG]) or urine pregnancy test at screening.
    8. Women of childbearing potential (defined as: fertile, following menarche and until becoming postmenopausal unless permanently sterile):
    a. Must be practicing a highly-effective method of birth control (failure rate of <1% per year when used consistently and correctly) during treatment and for 3 months after the last dose of study drug. Examples of highly effective methods of contraception are located in Appendix 6 of the protocol.
    b. Must agree to not donate eggs (ova, oocytes) for the purposes of assisted reproduction during treatment and for 3 months after the last dose of study drug.
    c. Must not be breastfeeding and not planning to become pregnant during treatment and for 3 months after the last dose of study drug.
    9. Men who are sexually active with women of childbearing potential and have not had a vasectomy, must:
    a. Agree to use a barrier method of birth control (eg, either condom with spermicidal foam/gel/film/cream/suppository or partner with occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository) during treatment and for 3 months after the last dose of study drug
    b. Agree to not donate sperm during treatment and for 3 months after the last dose of study drug
    c. Not plan to father a child during treatment or within 3 months after the last dose of study drug
    10. The potential subject or a legally authorized representative must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate.
    E.4Principal exclusion criteria
    Any potential subject who meets any of the following criteria will be excluded from participating in the study:
    1. Received prior HSCT or any prior treatment, including HMAs, for higher-risk MDS or CMML. Prior supportive therapies including transfusion and growth factors are acceptable.
    2. Received prior treatment with cusatuzumab.
    3. Presence of any of the following genetic abnormalities regardless of blast count:
    a. t(8;21)(q22;q22); RUNX1-RUNX1T1 (previously AML1-ETO)
    b. inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11
    c. t(15;17)(q22;q21.1); PML-RARA
    4. Presence of the bcr-abl rearrangement (ie, Philadelphia chromosome).
    5. Received a live, attenuated vaccine within 4 weeks prior to initiation of study drug.
    6. Active malignancies (ie, progressing or requiring treatment change in the last 24 months) other than the disease being treated under study. The only allowed exceptions are:
    a. Non-muscle invasive bladder cancer
    b. Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured
    c. Non-invasive cervical cancer treated within the last 24 months that is considered completely cured.
    d. Localized prostate cancer (N0M0):
    • With a Gleason score of 6, treated within the last 24 months or untreated and under surveillance
    • With a Gleason score of 3+4 that has been treated more than 6 months prior to full study screening and considered to have a very low risk of recurrence
    • Or history of localized prostate cancer (N0M0) and receiving androgen deprivation therapy and considered to have a very low risk of recurrence
    e. Breast cancer:
    • Adequately treated lobular carcinoma in situ or ductal carcinoma in situ
    • Or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence
    f. Malignancy that is considered cured with minimal risk of recurrence.
    7. Any active systemic infection.
    8. History of human immunodeficiency virus (HIV) antibody positive or tests positive for HIV at screening.
    9. Known hepatitis C infection or positive serologic testing for hepatitis C (anti-hepatitis C virus antibody).
    10. Seropositive for hepatitis B, defined by a positive test for hepatitis B surface antigen [HBsAg]. Subjects with resolved infection (ie, subjects who are HBsAg negative with antibodies to total hepatitis B core antigen [anti-HBc] with or without the presence of hepatitis B surface antibody [anti-HBs]) must be screened using real-time polymerase chain reaction (RT-PCR) measurement of hepatitis B virus (HBV) DNA levels. Those who are RT-PCR positive will be excluded. Subjects with serologic findings suggestive of HBV vaccination (ie, anti-HBs positivity as the only serologic marker) and a known history of prior HBV vaccination do not need to be tested for HBV DNA by RT-PCR.
    11. New York Heart Association Class 4 heart failure or ongoing unstable angina.
    12. Known allergies, hypersensitivity, or intolerance to cusatuzumab, azacitidine, or their excipients (eg, mannitol, an excipient of azacitidine).
    13. Any condition for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the well-being) or physical limitations that could prevent, limit, or confound the protocol-specified assessments.
    14. Major surgery (eg, requiring general anesthesia) within 4 weeks prior to initiation of study treatment.
    E.5 End points
    E.5.1Primary end point(s)
    Overall response rate (ORR) (rate of Complete remission [CR] + partial remission [PR] + marrow complete remission [mCR]), per modified International Working Group (IWG) criteria
    E.5.1.1Timepoint(s) of evaluation of this end point
    1. Within 14 days of Cycle (C)1 Day (D)1; Cycles 4, 8, and 12, then every 6 cycles until disease relapse from CR, PR, or mCR; progression; or transformation to AML or death, End of treatment
    E.5.2Secondary end point(s)
    1. a) CR + PR rate, per modified IWG criteria
    b) CR rate, per modified IWG criteria
    c) Time to response for subjects who achieved such responses, defined as time from randomization to achieving the first response of CR, PR, or mCR, per modified IWG criteria
    d) Time from achieving the first response of CR, PR, or mCR to relapse or death from any cause for those subjects who responded
    e) Transfusion independence, defined as a period of ≥56 consecutive days with no transfusion occurring between the first and last dose of study drug +30 days
    f) Transformation to AML, defined as ≥20% bone marrow blasts
    g) Progression-free survival (PFS), defined as the time from randomization to disease progression; relapse from CR, PR, or mCR; or death from any cause
    h) OS, defined as the time from randomization to death
    i) Hematologic improvement rate, per modified IWG criteria
    2. Safety parameters, including AEs and laboratory tests
    3. Proportion of subjects achieving a clinically meaningful improvement in Functional Assessment of Cancer Therapy-Anemia -Trial Outcome Index (FACT-An TOI)
    4. Serum concentration-time profile and PK parameters for cusatuzumab
    5. Characterization and quantification of anti-drug antibodies (ADAs)
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. Within 14 days of Cycle (C)1 Day (D)1; Cycles 4, 8, and 12, then every 6 cycles until relapse or disease progression; or transformation to AML or death, End of treatment
    2. Screening Day 1 of each 28 day cycle until 30 days after end of treatment or death
    3. C1D1; Cycles 4, 8 and 12, then every 6 cycles until relapse or disease progression, transformation to AML or death; End of treatment
    4. Screening, Cycle 1: Day 3, Day 4 and Day 17, C2D3, C3D3, C4D3, C4D21 to Cycle 5 Day 1 at disease evaluation, C8D3, C11D3, and End of treatment
    5. C1D3, C1D17, C2D3, C3D3, C4D3, C8D3, C11D3, and End of treatment
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity, Biomarker Evaluation, Patient-Reported Outcomes (PRO) Evaluation, Medical Resource Utilization Evaluation and Receptor Occupancy
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned9
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA90
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Brazil
    Czech Republic
    France
    Germany
    Italy
    Japan
    Russian Federation
    Saudi Arabia
    Spain
    Switzerland
    Turkey
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee No
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    The end of study (study completion) is defined as the time at which 50% of subjects have died or when the Sponsor decides to stop the study, whichever occurs first. The Sponsor will ensure that subjects benefiting from study treatment will be able to continue receiving study therapy.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days13
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months0
    E.8.9.2In all countries concerned by the trial days13
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 60
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 90
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Refer to protocol and informed consent form.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state15
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 90
    F.4.2.2In the whole clinical trial 150
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    The Sponsor will ensure that subjects benefiting from study treatment will be able to continue receiving study therapy.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2020-02-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2020-03-31
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2022-05-05
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