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    The EU Clinical Trials Register currently displays   43800   clinical trials with a EudraCT protocol, of which   7272   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:2014-000584-41
    Sponsor's Protocol Code Number:BP-004
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:
    Date on which this record was first entered in the EudraCT database:2015-07-15
    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 ConcernedUK - MHRA
    A.2EudraCT number2014-000584-41
    A.3Full title of the trial
    Phase I/II study of CaspaCide T cells from an HLA-partially matched family donor after negative selection of TCR αβ+ T cells in pediatric patients affected by hematological disorders
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase I/II study of CaspaCide T cells in children following αβ- depleted mis-matched family donor stem cell transplantation
    A.3.2Name or abbreviated title of the trial where available
    CaspaCide TCR αβ haplo HSCT
    A.4.1Sponsor's protocol code numberBP-004
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02065869
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/138/2017
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorBellicum Pharmaceuticals, Inc.
    B.1.3.4CountryUnited States
    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 supportBellicum Pharmaceuticals
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationBellicum Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointMaryam Ansari
    B.5.3 Address:
    B.5.3.1Street Address2710 Reed Road, Suite 160
    B.5.3.2Town/ cityHouston
    B.5.3.3Post codeTX 77051
    B.5.3.4CountryUnited States
    B.5.4Telephone number001346772 3263
    B.5.5Fax number001832384 1150
    B.5.6E-mailmansari@bellicum.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 Yes
    D.2.5.1Orphan drug designation numberEU/3/16/1674
    D.3 Description of the IMP
    D.3.1Product nameBPX-501 cells
    D.3.4Pharmaceutical form 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 INNRivogenlecleucel
    D.3.9.3Other descriptive nameBPX-501
    D.3.9.4EV Substance CodeSUB171410
    D.3.10 Strength
    D.3.10.1Concentration unit billion organisms/g billion organisms/gram
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number200 to 1000
    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) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Yes
    D.3.11.3.1Somatic cell therapy medicinal product Yes
    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 Yes
    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 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 Yes
    D.2.5.1Orphan drug designation numberEU/3/16/1666
    D.3 Description of the IMP
    D.3.1Product namerimiducid
    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 INNRimiducid
    D.3.9.1CAS number 195514-63-7
    D.3.9.3Other descriptive nameAP1903 A594
    D.3.9.4EV Substance CodeSUB171411
    D.3.10 Strength
    D.3.10.1Concentration unit mg/kg milligram(s)/kilogram
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.4
    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.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
    Hematological disorders (ALL; AML; Non-Hodgkin lymphoma; Myelodysplastic syndromes; Congenital immune deficiencies; Severe aplastic anemia; Fanconi anemia; Osteopetrosis; Selected cases of hemoglobinopathies)
    E.1.1.1Medical condition in easily understood language
    Hematological disorders
    E.1.1.2Therapeutic area Diseases [C] - Blood and lymphatic diseases [C15]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLGT
    E.1.2Classification code 10018849
    E.1.2Term Haematological disorders NEC
    E.1.2System Organ Class 10005329 - Blood and lymphatic system disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    This is a Phase I/II extension study evaluating the safety and feasibility of BPX-501 T cells infused after partially matched, related, T cell-depleted HSCT in pediatric patients. The purpose of this clinical trial is to determine whether BPX-501 infusion can enhance immune reconstitution in those patients with hematologic disorders, with the potential for reducing the severity and duration of severe acute GVHD, thereby improving overall survival. The trial will also evaluate the treatment of GVHD by the infusion of dimerizer drug (rimiducid), activating the safety gene, in those subjects who present with GVHD who do not respond to standard of care treatment.




    E.2.2Secondary objectives of the trial
    This study will look at how long the patient remains disease free following the transplantation, and how many patients relapse.
    To look at how many patients have recovery in the number blood cells called neutrophils and platelets.
    To assess transplant/graft failure.
    To assess graft versus host disease (GVHD)severity, how often GVHD occurs and the time it takes to recover following infusion of AP1903.
    To assess the infection complications.
    To assess time to recovery of patient’s immunity.
    To look at the duration of hospital admission.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Patient Inclusion Criteria:
    1. Males or females
    2. Age ≤ 18 years and ≥ 1 month (<1 month upon approval by Sponsor)
    3. Life expectancy > 10 weeks
    4. Patients deemed clinically eligible for allogeneic stem cell transplantation.
    5. Patients may have failed a prior allograft.
    6. Patients with life-threatening acute leukemia (high-risk Acute Lymphoblastic leukemia (ALL) in 1st Complete remission (CR), ALL in 2nd CR, high-risk Acute Myeloid leukemia (AML) in 1st CR, AML in 2nd CR). Morphological CR must be documented and minimal residual disease measurement before transplantation is recommended.
    7. Non-malignant disorders deemed curable by allogenic transplantation:
    a. primary immune deficiencies,
    b. severe aplastic anemia not responding to immune suppressive therapy,
    c. osteopetrosis,
    d. selected cases of erythoid disorders, such as β0 β0 thalassemia major, sickle cell disease, Diamond-Blackfan anemia,
    e. congenital/hereditary cytopenia, including Fanconi Anemia before any clonal malignant evolution (Myelodysplastic syndrome (MDS), AML).
    Note: subjects will be eligible if they meet either item 6 or 7.
    8. Lack of suitable conventional donor (Human Leucocyte Antigene (HLA) identical sibling or HLA phenotypically identical relative or 9-10/10 unrelated donor evaluated using high resolution molecular typing) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
    9. A minimum genotypic identical match of 5/10 is required
    10. The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA- DRB1 and HLA-DQB1.
    11. Lansky/Karnofsky score > 50
    12. Signed written informed consent by the patient or the patient's parent or guardian for patients who are minors

    Donor Inclusion criteria:
    1. Eligible donors include 5/10 HLA identical relative, including but not limited to biological parents, siblings, or half-siblings. Matching will be determined by class I and class II DNA typing. The donor of the BPX-501 T cells must be the HSCT donor.
    2. Donor age must be > 18 and < 65 years.
    3. The donor should be sufficiently healthy not to be at increased risk from the mobilization procedure.
    4. Should more than one “equally” MHC compatible donor be identified, other selection criteria may include natural killer cell (NK) alloreactivity, NK cell KIR-Haplotype, B-content for B-haplotype donors, size of the NK alloreactive subset, gender, age, CMV status, health status and body weight of donor. The physician treating the subject will make the final decision.
    5. Donors must meet the selection criteria as defined by the European Directive 2006/17/CE and according to the FACT-JACIE International Standards and local regulations for donor selection.
    6. The donor must have been informed of the investigational nature of the BPX-501 product and have signed an informed consent form that they will undergo a second pheresis procedure.
    7. Donor must have adequate peripheral venous access for leukapheresis or must agree to placement of a central venous catheter.
    8. The collection of donor T cells to be transduced with the suicide gene will be performed before the mobilization procedure with G-CSF in order to avoid any potential negative influence of this cytokine on function of genetically modified T cells.
    9. Signed informed consent
    E.4Principal exclusion criteria
    Patient Exclusion criteria:
    1. Greater than grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of inclusion
    2. Patient receiving an immunosuppressive treatment for GVHD treatment due o a previous allograft at the time of inclusion
    3. Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance < 30 ml / min)
    4. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction <40%)
    5. Current uncontrolled clinically active infectious disease (including positive HIV serology or viral RNA
    6. Serious concurrent uncontrolled medical disorder
    7. Pregnant or breast feeding female patient
    8. Lack of parents'/guardian's informed consent

    Donor exclusion criteria
    1. Evidence of active infection (including urinary tract infection, or upper respiratory tract infection) or viral hepatitis exposure (on screening), unless HBs Ab+ and HBV DNA negative.
    2. Factors which place the donor at increased risk for complications from leukapheresis or G-CSF therapy (e.g., autoimmune disease, sickle cell trait, symptomatic coronary artery disease requiring therapy, previous thrombotic events).
    3. Pregnancy at the time of normal leukapheresis for the T cells and at the time of the mobilization for the stem cell allograft collection.
    4. Breastfeeding at the time of mobilization

    Sponsor will be notified of any AEs (infections, etc.) occurring in the donor between the leukapheresis and stem cell apheresis.
    E.5 End points
    E.5.1Primary end point(s)
    Phase I dose escalation summary
    Nine subjects were treated according to a 3+3 dose escalation design. Cohorts 1-3 subjects received 0.2 X106 BPX-501 T cells/kg, 0.5 X 106 BPX-501 T cells/kg, and 1 X 106 BPX-501 T cells/kg, respectively. No DLTs were observed and the study then continued at the highest tested dose, namely 1 X 106 BPX-501 T cells/kg. No related AEs or SAEs were reported. There were no dose-limiting toxicities. All 9 subjects showed evidence of BPX-501 T cells. Subjects experienced Grade II skin-only GvHD which resolved without treatment with rimiducid.
    The Phase II extension study will evaluate the 1x106 BPX-501 T cells/kg dose for both malignant and non-malignant diseases.

    Phase II primary end-points
    Event-Free Survival at 180 days (events include TRM (or NRM for malignant patients), severe GvHD (acute Grade 2-4 organ or extensive GvHD) and life threatening infections (Grade 4)
    E.5.1.1Timepoint(s) of evaluation of this end point
    Up to 24 months post-transplant
    E.5.2Secondary end point(s)
    TRM (non-malignant) or NRM (malignant) at 100 and 180 days.
    Cumulative incidence and severity of acute (grade 2-4) and chronic GVHD at 180 days.
    Time to resolution of acute or chronic GVHD after administration of rimiducid.
    Immune reconstitution as determined by T cell subsets at day 180:
    a) Absolute CD3 count
    b) Absolute CD4 count
    c) Absolute CD8 count
    Time to immune reconstitution.
    Disease Free/cGVHD survival at 180 days.
    Disease status of each specific disease indication at 180 days:
    a) Primary immune disorders as determined by CD3 T cell count >500 cells/ul and lower normal levels of IgA and IgM at 180 days.
    b) Haemoglobinopathies as determined by incidence of RBC transfusion dependence and haemoglobin of >8.5 g/dL at 180 days.
    c) Fanconi Anemia as determined by RBC >3,000,000 cells/ul, neutrophil count determined by 1500 cells/ul and >150,000 platelet counts at 180 days.
    d) Leukemia as determined by PFS at 180 days.
    E.5.2.1Timepoint(s) of evaluation of this end point
    For a period of 15 years.
    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 Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    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) 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 No
    E.8.1.2Open No
    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.8.3 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 concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA4
    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 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 study will evaluate overall survival and disease free survival for all patients enrolled at 24 months after transplantation. The study will be closed after the completion of the 15 years of follow-up.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years15
    E.8.9.1In the Member State concerned months0
    E.8.9.1In the Member State concerned days1
    E.8.9.2In all countries concerned by the trial years15
    E.8.9.2In all countries concerned by the trial months7
    E.8.9.2In all countries concerned by the trial days18
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 175
    F.1.1.1In Utero No
    F.1.1.1.1Number of subjects for this age range: 0
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.2.1Number of subjects for this age range: 0
    F.1.1.3Newborns (0-27 days) No
    F.1.1.3.1Number of subjects for this age range: 0
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 60
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 80
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 30
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 5
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    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
    Children
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 175
    F.4.2.2In the whole clinical trial 175
    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 - Not applicable
    G. Investigator Networks to be involved in the Trial
    G.4 Investigator Network to be involved in the Trial: 1
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2015-03-24
    N.Ethics Committee Opinion of the trial application
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion
    P. End of Trial
    P.End of Trial Status
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