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Trial record 1 of 1 for:    ALLCAR19
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Immunotherapy for High Risk/Relapsed CD19+ Acute Lymphoblastic Leukaemia Using CAR T-cells to Target CD19 (ALLCAR19)

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ClinicalTrials.gov Identifier: NCT02935257
Recruitment Status : Recruiting
First Posted : October 17, 2016
Last Update Posted : October 16, 2018
Sponsor:
Information provided by (Responsible Party):
University College, London

Brief Summary:

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age 16 to 65 years) with high risk, relapsed/refractory CD19+ B-ALL. The ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with a lentiviral vector to generate the CD19CAT-41BBZ CAR T-cells (referred to subsequently as CD19CAR T-cells). Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP which will take approximately 15 days to generate. During this period, patients may receive "holding" chemotherapy as per institutional practice to maintain disease control. Patients will receive pre-conditioning lymphodepleting chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3).

The study is designed as an intra-patient dose escalation employing a total dose range (over 2 doses, Dose 1 and Dose 2) of between 5 x 106 CD19CAR T-cells and 1.1 x 109 CD19CAR T-cells. The study will evaluate ATIMP safety and efficacy and the duration of disease response in adults with high risk / relapsed CD19+ B-ALL.

After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, will enter long term follow up until 5 years post-CD19CAR T-cell infusion.


Condition or disease Intervention/treatment Phase
Leukemia, Lymphoblastic, Acute Biological: CD19CAT-41BBZ CAR T-cells Phase 1

Detailed Description:

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age 16 to 65 years) with high risk, relapsed/refractory CD19+ B-ALL. The ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with a lentiviral vector to generate the CD19CAT-41BBZ CAR T-cells (referred to subsequently as CD19CAR T-cells). Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP which will take approximately 15 days to generate. During this period, patients may receive "holding" chemotherapy as per institutional practice to maintain disease control. Patients will receive pre-conditioning lymphodepleting (LD) chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3).

The study is designed as an intra-patient dose escalation employing a total dose range (over 2 doses, Dose 1 and Dose 2) of between (minimum) 5 x 106 CD19CAR T-cells (plus 20% for thawing losses) and (maximum) 1.1 x 109 CD19CAR T-cells (plus 20% for thawing losses).

The initial ATIMP dose administered is dependent upon B-ALL disease burden in the bone marrow. For patients with <20% marrow infiltration by B-ALL at baseline (screening), Dose 1a will be 1x108 CD19CAR T-cells and will be administered on Day 0 following LD. For those with ≥20% marrow infiltration by B-ALL, Dose 1b, administered on Day 0, will be 1x107 CD19CAR T-cells. This measure to prevent toxicity is in keeping with published data correlating severity of CRS with disease burden.

Dose 1a* (BM blasts≤20%): 1x108 CD19CAR T-cells (plus 20% for thawing losses) Dose 1b* (BM blasts>20%): 1x107 CD19CAR T-cells (plus 20% for thawing losses) Dose 2* (all patients, in the absence of clinically severe CRS): dosing range between minimum dose of ≥5 x 106 CD19CAR T-cells (plus 20% for thawing losses) and maximum dose of ≤1x109 CD19CAR T-cells (plus 20% for thawing losses)

*Minimum dose permitted on trial at all Dose levels is ≥5 x 106 CD19CAR T-cells (plus 20% for thawing losses) The study will evaluate ATIMP safety and efficacy and the duration of disease response in adults with high risk / relapsed CD19+ B-ALL. After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, will enter long term follow up until 5 years post-CD19CAR T-cell infusion.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Immunotherapy for High Risk/Relapsed CD19+ Acute Lymphoblastic Leukaemia
Actual Study Start Date : September 29, 2017
Estimated Primary Completion Date : April 2020
Estimated Study Completion Date : November 2024


Arm Intervention/treatment
Experimental: CD19CAT-41BBZ CAR T-cells
Treatment with the ATIMP: CD19CAT-41BBZ CAR T-cells
Biological: CD19CAT-41BBZ CAR T-cells
Infusion with CD19CAT-41BBZ CAR T-cells




Primary Outcome Measures :
  1. Toxicity evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP [ Time Frame: 30 days ]
    Toxicity following CD19CAR T-cell administration as evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP.

  2. Feasibility of manufacturing CD19CAR T-cells evaluated by the number of therapeutic products generated [ Time Frame: 30 days ]
    Feasibility of adequate leucapheresis collection and generation of CAR19 T cells as evaluated by the number of therapeutic products generated.



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adults (age range 16 to 65 years) with high risk/relapsed histologically confirmed CD19+ B-ALL following standard therapy with measurable disease requiring salvage and in whom alternative therapies are deemed inappropriate by their treating physician.
  2. Agreement to have a pregnancy test, use adequate contraception (if applicable)
  3. Written informed consent

Exclusion Criteria:

  1. CD19 negative disease
  2. Overt CNS involvement (ie: patients with CNS2 with neurological symptoms or patients with CNS3)
  3. Isolated extramedullary disease
  4. Active hepatitis B, C or HIV infection
  5. Oxygen saturation ≤ 90% on air
  6. Bilirubin > 2 x upper limit of normal
  7. GFR>50ml/min
  8. Women who are pregnant or breast feeding
  9. Stem Cell Transplant patients only: active significant acute GVHD (overall Grade ≥ II, Seattle criteria) or moderate/severe chronic GVHD (NIH consensus criteria) requiring immunosuppressive therapy and/or systemic steroids
  10. Inability to tolerate leucapheresis
  11. Karnofsky score<60% (see appendix 3)
  12. Patients who have experienced significant neurotoxicity following blinatumomab
  13. Known allergy to albumin or DMSO
  14. Life expectancy <3months
  15. Arrythmias or significant cardiac disease and LVEF <40%
  16. Pre-existing neurological disorders (other than CNS involvement of underlying haematological malignancy)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02935257


Contacts
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Contact: Bilyana Popova 02076799860 ctc.allcar19@ucl.ac.uk

Locations
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United Kingdom
University College London Hospital Recruiting
London, United Kingdom
Contact: Prof. Karl Peggs         
Principal Investigator: Prof. Karl Peggs         
Sponsors and Collaborators
University College, London
Investigators
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Study Chair: Karl Peggs University College London Hospitals

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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT02935257     History of Changes
Other Study ID Numbers: UCL/16/0530
First Posted: October 17, 2016    Key Record Dates
Last Update Posted: October 16, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
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Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases