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    The EU Clinical Trials Register currently displays   43925   clinical trials with a EudraCT protocol, of which   7306   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2021-000853-17
    Sponsor's Protocol Code Number:DKMS-21-01
    National Competent Authority:Germany - BfArM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2021-07-08
    Trial 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 ConcernedGermany - BfArM
    A.2EudraCT number2021-000853-17
    A.3Full title of the trial
    Graft vs Host Disease Prophylaxis in unrelated donor transplantation: a randomized clinical trial comparing PTCY vs ATG
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Randomized comparison of Cyclophosphamide and ATG for prophylaxis of GvHD after unrelated donor transplantation
    Randomisierter Vergleich von Cyclophosphamid und ATG zur Vorbeugung von GvHD nach unverwandter Blutstammzelltransplantation
    A.3.2Name or abbreviated title of the trial where available
    GRAPPA
    A.4.1Sponsor's protocol code numberDKMS-21-01
    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 SponsorDKMS Group gGmbH
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportDKMS Group gGmbH
    B.4.2CountryGermany
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationDKMS Group gGmbH
    B.5.2Functional name of contact pointClinical Trials Unit
    B.5.3 Address:
    B.5.3.1Street AddressAugsburger Str. 3
    B.5.3.2Town/ cityDresden
    B.5.3.3Post code01309
    B.5.3.4CountryGermany
    B.5.6E-mailgrappa@dkms.de
    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 Yes
    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.3.4Pharmaceutical form Powder for solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMP
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNCYCLOPHOSPHAMIDE
    D.3.9.1CAS number 50-18-0
    D.3.9.4EV Substance CodeSUB06859MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    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 No
    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.IMP: 2
    D.1.2 and D.1.3IMP RoleComparator
    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 Yes
    D.2.1.1.1Trade name Grafalon 20 mg/ml
    D.2.1.1.2Name of the Marketing Authorisation holderNeovii Biotech GmbH
    D.2.1.2Country which granted the Marketing AuthorisationGermany
    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.3.4Pharmaceutical form Concentrate for solution for infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInfusion (Noncurrent)
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNANTI-HUMAN T-LYMPHOCYTE IMMUNOGLOBULIN FROM RABBIT
    D.3.9.3Other descriptive nameANTI-T LYMPHOCYTE IMMUNOGLOBULIN FOR HUMAN USE, RABBIT
    D.3.9.4EV Substance CodeSUB21246
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    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
    AML, t-MN, MDS, MDS/MPN, CMML-1/CMML-2
    E.1.1.1Medical condition in easily understood language
    AML, t-MN, MDS, MDS/MPN, CMML-1/CMML-2
    E.1.1.2Therapeutic area Diseases [C] - Cancer [C04]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    One of the key elements to improve allogeneic HCT is the administration of optimized conditioning treatment including immunosuppressive drugs to facilitate engraftment, prevent GVHD and induce tolerance of donor immune cells.
    Specifically the goal of this trial is:
    1. to investigate the impact of PTCY versus ATG-Grafalon as part of a conditioning treatment for alloHCT on overall survival.
    2. to investigate the potential of PTCY versus ATG-Grafalon to allow for disease-free and immunosuppression-free survival one year after alloHCT.
    Information on the investigational drugs provided by these two endpoints will enable the scientific community a comprehensive assessment of the two approaches for alloHCT.
    E.2.2Secondary objectives of the trial
    Data collected within this trial will further allow:
    − to assess the risk of acute and chronic GVHD, relapse and NRM after alloHCT per treatment arm
    − to evaluate risk factors for acute and chronic GVHD, relapse, and NRM.
    − to test for interactions between the presence or absence of (specific) HLA mismatches and major alloHCT outcomes.
    − to test for interactions between sex mismatches and major alloHCT outcomes.
    − to describe organ-specific clinical patterns of GVHD depending on the study arm.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    − Signed written Informed Consent and able to understand the nature of the trial and the trial related procedures and to comply with them (see Section 24.3).
    − Age ≥ 18 years.
    − One of the following eligible diagnoses:
    - AML in CR1 with intermediate or adverse risk genetic abnormalities (according to the ELN 2022 guidelines), or undefined risk.
    - AML of any ELN risk category after hematological or molecular relapse, or with primary refractory disease.
    - AML arising from myelodysplastic syndrome (MDS) or a myeloproliferative neoplasia, except if favourable genetic abnormalities (according to ELN 2022 guidelines) are present.
    - Therapy-related myeloid neoplasia (t-MN), except if favourable genetic abnormalities (according to ELN 2022 guidelines) are present.
    - MDS with intermediate risk, high risk or very high risk disease according to the IPSS-R Score or MDS with moderate high, high, or very high risk disease according to the IPSS-M Score regardless of treatment status.
    - MDS/MPN and CMML-1/CMML-2 according to WHO 2022 regardless of treatment status.
    − The left ventricular ejection fraction (LVEF) was ≥40% at last assessement.
    − Planned transplantation with Peripheral Blood Stem Cells (PBSC).
    − Transplantation scheduled to be performed 4 to 14 days after date of randomization.
    − The scheduled donor is unrelated to the patient, and matched or partially matched (with not more than one allele or antigen mismatch) at HLA-A, -B, -C, or -DRB1.
    − Absence of pregnancy confirmed by highly sensitive pregnancy test for WOCBP (see Section 17.6). Test must not date back
    - more than 3 days prior to randomization, or
    - more than 3 days prior to start of conditioning, if it started before randomization.
    E.4Principal exclusion criteria
    − Anamnestic intravenous or subcutaneous exposure to rabbit immunoglobin-preparations (e.g. Grafalon or Thymoglobulin)
    − Known hypersensitivity to ATG-Grafalon or its excipients.
    − Known hypersensitivity to cyclophosphamide, its metabolites or excipients.
    − Prior allogeneic hematopoietic transplantation.
    − Patients who receive supplementary continuous oxygen at the time of randomization.
    − Symptomatic heart failure (NYHA ≥2) at the time of randomization.
    − Uncontrolled viral, bacterial or fungal infection with progression or no clinical improvement at the time of randomization.
    − Symptomatic cystitis or known obstruction of urine flow at the time of randomization.
    − Breast-feeding women.
    − WOCBP and fertile male patients unable or unwilling to follow highly effective contraception methods from enrollment to minimum six months after the last dose of the IMP (see Section 17.6).
    − Simultaneous participation in another interventional clinical trial with an investigational medicinal product.
    E.5 End points
    E.5.1Primary end point(s)
    overall survival (OS) from time of transplantation (across the whole observational period), and
    relapse- and immunosuppression-free survival (RIFS) at 1 year from time of transplantation.
    E.5.1.1Timepoint(s) of evaluation of this end point
    please refer to the combined information given in E.5.1
    E.5.2Secondary end point(s)
    − GVHD- and relapse-free survival (GRFS, events: onset of aGVHD III-IV or cGVHD requiring immunosuppressive treatment, death, relapse).
    − Event-free survival (EFS, events: relapse and death) from HCT.
    − Cumulative incidences of relapse from HCT.
    − Cumulative incidences of non-relapse mortality (NRM) from HCT.
    − Cumulative incidences of aGVHD grades II-IV during the first 180 days from HCT.
    − Cumulative incidences of aGVHD grades III-IV during the first 180 days from HCT.
    − Cumulative incidences of cGVHD during first 2 years from HCT.
    − Cumulative incidences of severe cGVHD during the first 2 years from HCT.
    − Rate of complete remission without measurable residual disease until Day 56 from HCT.
    − Rate of engraftment failure until Day 56 from HCT.
    − Rate of patients requiring intensive care (organ replacement therapy) by Day 56 from HCT.
    − Cumulative incidence of CMV reactivations during first 180 days from HCT.
    E.5.2.1Timepoint(s) of evaluation of this end point
    please refer to the combined information given in E.5.2.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    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 Yes
    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) Yes
    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 concerned25
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    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
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    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: 540
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 540
    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 No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state540
    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)
    None
    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 Decision2021-11-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-11-11
    P. End of Trial
    P.End of Trial StatusOngoing
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