免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Intravenous Autologous CD19 CAR-T Cells for R/R B-ALL

Intravenous Autologous CD19 CAR-T Cells for R/R B-ALL

Study Description
Brief Summary:
This is Phase II / III, Prospective, single arm, Open Label Study to Evaluate Safety and Efficacy of Intravenous Autologous CD19 CAR-T Cells for Relapsed / Refractory B-Acute Lymphoblastic Leukaemia

Condition or disease Intervention/treatment Phase
Relapsed B Acute Lymphoblastic Leukaemia Refractory B Acute Lymphoblastic Leukaemia Biological: CD19 CAR-T CELLS Drug: Cyclophosphamide Drug: Fludarabine Phase 2 Phase 3

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II/III Prospective, Open Label Study to Evaluate Safety and Efficacy of Intravenous Autologous CD19 CAR-T Cells for Relapsed/ Refractory B-Acute Lymphoblastic Leukaemia
Actual Study Start Date : March 19, 2019
Estimated Primary Completion Date : March 18, 2024
Estimated Study Completion Date : March 18, 2024
Arms and Interventions
Arm Intervention/treatment
Experimental: CD19 CAR-T CELLS
A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
 Biological: CD19 CAR-T CELLS
CD19 CAR-T cells will be administered after completion of the chemotherapy.

Drug: Cyclophosphamide
Patients will receive lymphodepleting chemotherapies consisting Cyclophosphamide 250mg/m2/day IV(Day -5, Day -4, Day -3 ).

Drug: Fludarabine
Patients will receive lymphodepleting chemotherapies consisting of Fludarabine 25mg/m2/day IV (Day -5, Day -4, Day -3 ).
Outcome Measures
Primary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: Participants will be followed for the duration of the treatment, with an expected average of 3 months. ]
    Overall Response Rate (ORR) defined as Complete Response (CR) and CR with incomplete blood recovery (CRi) according to WHO criteria.

  2. Complete response (CR) [ Time Frame: 12 Months ]
    Duration of response defined from the time when criteria for response (CR or CRi) are met to the first documentation of relapse or progression.

  3. CR with incomplete blood recovery (CRi). [ Time Frame: 12 Months ]
    Duration of response defined from the time when criteria for response (CR or CRi) are met to the first documentation of relapse or progression.


Secondary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 12 Months, 24 Months ]
    Overall Survival (OS) defined as the time from treatment to the date of death due to any cause.

  2. Progression free survival (PFS) [ Time Frame: 12 Months, 24 Months ]
    Progression Free Survival (PFS) defined as the time from treatment to first documentation of objective leukemic progression (date of leukaemia assessment documenting progressive disease) or to death due to any cause. Progression is assessed by BM biopsy or CSF analysis according to NCCN criteria. It is assessed at Day 30 and monthly thereafter, or earlier if clinically indicated.

  3. Time to next treatment (TTNT) [ Time Frame: 12 Months, 24 Months ]
    Time To Next Treatment (TTNT) defined as the end of study treatment until the institution of the next therapy.

  4. Percentage of adverse events [ Time Frame: 30 days ]
    Percentage of participants with adverse events


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   13 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with relapsed/refractory B-ALL in accordance with World Health Organization (WHO) classification by virtue of BM morphology, flow cytometry, cytogenetics and molecular genetics
  • Age between ≥13 to ≤ 65 years
  • No detectable leukaemia in the CSF (CNS-1)
  • CNS leukaemia without clinically evident neurological symptoms (CNS-2; with <5 WBC per μL and cytology positive for blasts)
  • Adequate organ function as defined by a creatinine clearance > 50 ml/min, serum total bilirubin < 5 times the normal value, left ventricular ejection fraction > 40%
  • ECOG performance status ≤ 2
  • Life expectancy > 3 months
  • Post allogeneic HSCT must be ≥ Day +100 with no evidence of active GVHD and not receiving immunosuppression
  • Female patients of child bearing age must have negative pregnancy test and is on highly effective contraception methods
  • Male patients must use highly effective contraception methods

Exclusion Criteria:

  • Patients with CNS-3 leukaemia.
  • Active cancer (other than B-ALL).
  • Evidence of severe lung, heart (NYHA class III/IV, arrhythmia, AV block, uncontrolled hypertension), liver, or renal failure or severe neurologic disorder.
  • Presence of active autoimmune disease or atopic allergy.
  • HIV serology positivity.
  • Active Hepatitis B or C infection as evidenced by quantitative viral PCR assay.
  • Uncontrolled sepsis
  • Pregnant / nursing female.
  • Ongoing prednisolone > 1mg/kg daily or equivalent.
  • Chemotherapy immunotherapy in the recent 4 weeks such as allogeneic cellular therapy weeks, anti-GVHD therapy.
Contacts and Locations

Contacts
Layout table for location contacts
Contact: S Fadilah Abdul Wahid, MD, DrIntMed, PhD +60391456450 sfadilah@ppukm.ukm.edu.my

Locations
Layout table for location information
Malaysia
UKM Medical Centre Recruiting
Bandar Tun Razak, Kuala Lumpur, Malaysia, 56000
Contact: S Fadilah Abdul Wahid, MD, DrIntMed, PhD    +60391456450    sfadilah@ppukm.ukm.edu.my   
Contact: Wan Fariza Wan Jamaludin, MD,DrIntMed    +60391457709    wanfariza@ppukm.ukm.edu.my   
Sponsors and Collaborators
National University of Malaysia
Gaia Science
Tracking Information
First Submitted Date  ICMJE April 22, 2019
First Posted Date  ICMJE May 3, 2019
Last Update Posted Date May 6, 2019
Actual Study Start Date  ICMJE March 19, 2019
Estimated Primary Completion Date March 18, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
  • Overall response rate (ORR) [ Time Frame: Participants will be followed for the duration of the treatment, with an expected average of 3 months. ]
    Overall Response Rate (ORR) defined as Complete Response (CR) and CR with incomplete blood recovery (CRi) according to WHO criteria.
  • Complete response (CR) [ Time Frame: 12 Months ]
    Duration of response defined from the time when criteria for response (CR or CRi) are met to the first documentation of relapse or progression.
  • CR with incomplete blood recovery (CRi). [ Time Frame: 12 Months ]
    Duration of response defined from the time when criteria for response (CR or CRi) are met to the first documentation of relapse or progression.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 1, 2019)
  • Overall survival (OS) [ Time Frame: 12 Months, 24 Months ]
    Overall Survival (OS) defined as the time from treatment to the date of death due to any cause.
  • Progression free survival (PFS) [ Time Frame: 12 Months, 24 Months ]
    Progression Free Survival (PFS) defined as the time from treatment to first documentation of objective leukemic progression (date of leukaemia assessment documenting progressive disease) or to death due to any cause. Progression is assessed by BM biopsy or CSF analysis according to NCCN criteria. It is assessed at Day 30 and monthly thereafter, or earlier if clinically indicated.
  • Time to next treatment (TTNT) [ Time Frame: 12 Months, 24 Months ]
    Time To Next Treatment (TTNT) defined as the end of study treatment until the institution of the next therapy.
  • Percentage of adverse events [ Time Frame: 30 days ]
    Percentage of participants with adverse events
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Intravenous Autologous CD19 CAR-T Cells for R/R B-ALL
Official Title  ICMJE A Phase II/III Prospective, Open Label Study to Evaluate Safety and Efficacy of Intravenous Autologous CD19 CAR-T Cells for Relapsed/ Refractory B-Acute Lymphoblastic Leukaemia
Brief Summary This is Phase II / III, Prospective, single arm, Open Label Study to Evaluate Safety and Efficacy of Intravenous Autologous CD19 CAR-T Cells for Relapsed / Refractory B-Acute Lymphoblastic Leukaemia
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Relapsed B Acute Lymphoblastic Leukaemia
  • Refractory B Acute Lymphoblastic Leukaemia
Intervention  ICMJE
  • Biological: CD19 CAR-T CELLS
    CD19 CAR-T cells will be administered after completion of the chemotherapy.
  • Drug: Cyclophosphamide
    Patients will receive lymphodepleting chemotherapies consisting Cyclophosphamide 250mg/m2/day IV(Day -5, Day -4, Day -3 ).
  • Drug: Fludarabine
    Patients will receive lymphodepleting chemotherapies consisting of Fludarabine 25mg/m2/day IV (Day -5, Day -4, Day -3 ).
Study Arms  ICMJE Experimental: CD19 CAR-T CELLS
A conditioning chemotherapy regiment of fludarabine and cyclophosphamide will be administered followed by a single infusion of CAR transduced autologous T cells administered intravenously.
Interventions:
  • Biological: CD19 CAR-T CELLS
  • Drug: Cyclophosphamide
  • Drug: Fludarabine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 1, 2019) 		10
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 18, 2024
Estimated Primary Completion Date March 18, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with relapsed/refractory B-ALL in accordance with World Health Organization (WHO) classification by virtue of BM morphology, flow cytometry, cytogenetics and molecular genetics
  • Age between ≥13 to ≤ 65 years
  • No detectable leukaemia in the CSF (CNS-1)
  • CNS leukaemia without clinically evident neurological symptoms (CNS-2; with <5 WBC per μL and cytology positive for blasts)
  • Adequate organ function as defined by a creatinine clearance > 50 ml/min, serum total bilirubin < 5 times the normal value, left ventricular ejection fraction > 40%
  • ECOG performance status ≤ 2
  • Life expectancy > 3 months
  • Post allogeneic HSCT must be ≥ Day +100 with no evidence of active GVHD and not receiving immunosuppression
  • Female patients of child bearing age must have negative pregnancy test and is on highly effective contraception methods
  • Male patients must use highly effective contraception methods

Exclusion Criteria:

  • Patients with CNS-3 leukaemia.
  • Active cancer (other than B-ALL).
  • Evidence of severe lung, heart (NYHA class III/IV, arrhythmia, AV block, uncontrolled hypertension), liver, or renal failure or severe neurologic disorder.
  • Presence of active autoimmune disease or atopic allergy.
  • HIV serology positivity.
  • Active Hepatitis B or C infection as evidenced by quantitative viral PCR assay.
  • Uncontrolled sepsis
  • Pregnant / nursing female.
  • Ongoing prednisolone > 1mg/kg daily or equivalent.
  • Chemotherapy immunotherapy in the recent 4 weeks such as allogeneic cellular therapy weeks, anti-GVHD therapy.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 13 Years to 65 Years   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: S Fadilah Abdul Wahid, MD, DrIntMed, PhD +60391456450 sfadilah@ppukm.ukm.edu.my
Listed Location Countries  ICMJE Malaysia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03937544
Other Study ID Numbers  ICMJE JEP-2019-003
FF-2019-138 ( Other Identifier: UKM Medical Centre )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Prof. Dr S Fadilah Abdul Wahid, National University of Malaysia
Study Sponsor  ICMJE National University of Malaysia
Collaborators  ICMJE Gaia Science
Investigators  ICMJE Not Provided
PRS Account National University of Malaysia
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

治疗案例

前沿医讯