NCT03298828

Brief Summary

The purpose of this study is to evaluate the safety, efficacy and blood kinetics of autologous T cells genetically modified to express CD19 Chimeric Antigen Receptor and PD-1 knockout engineered T cells in patients with relapsed or refractory B-Cell Non-Hodgkin Lymphoma and Leukaemia.

Trial Health

35
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
30

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2017

Longer than P75 for phase_1

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 24, 2017

Completed
2 months until next milestone

First Posted

Study publicly available on registry

October 2, 2017

Completed
1 month until next milestone

Study Start

First participant enrolled

November 1, 2017

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2020

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2022

Completed
Last Updated

October 2, 2017

Status Verified

September 1, 2017

Enrollment Period

2.9 years

First QC Date

July 24, 2017

Last Update Submit

September 26, 2017

Conditions

Acute Lymphoblastic LeukemiaBurkitt Lymphoma

Outcome Measures

Primary Outcomes (1)

  • Molecular remission

    Efficacy will be assessed by determining Minimal Residual Disease in the bone marrow aspirate using immunoglobulin heavy chain (IgH) quantitative polymerase chain reaction (qPCR) and/or Next Generation Sequencing in all patients. The proportion of patients achieving molecular remission at 1 month post CD19 CAR and PD-1 Knockout Engineered T-cell infusion will be determined.

    1 month

Secondary Outcomes (5)

  • Long term molecular remission

    2 years

  • Frequency of circulating CD19 CAR and PD-1 Knockout Engineered T-cells

    2 years

  • Incidence of hypogammaglobulinaemia

    2 years

  • Relapse rate

    10 years

  • Overall Survival

    10 years

Study Arms (2)

CD19 CAR

EXPERIMENTAL

Patients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19 CAR T-cells. Patients will receive lymphodepletion with fludarabine and cyclophosphamide prior to infusion of the CD19 CAR T-cells.

Biological: CD19 CAR T-cells

CD19 CAR and PD-1 knock out

EXPERIMENTAL

Patients meeting the eligibility criteria will have leukapheresis to isolate the blood immune cells used to manufacture the CD19 CAR and PD-1 knock out engineered T-cells. Patients will receive lymphodepletion with fludarabine and cyclophosphamide prior to infusion of the CD19 CAR and PD-1 knock out engineered T-cells.

Biological: CD19 CAR and PD-1 knock out engineered T-cells

Interventions

CD19 CAR and PD-1 knock out engineered T-cellsBIOLOGICAL

A single dose of 1 x 10\^6/kg CD19 CAR transduced and PD-1 knock out engineered T-cells will be given as an intravenous injection through a Hickman line or PICC line(peripherally inserted central catheter) on day 0.

CD19 CAR and PD-1 knock out
CD19 CAR T-cellsBIOLOGICAL

A single dose of 1 x 10\^6/kg CD19 CAR transduced T-cells will be given as an intravenous injection through a Hickman line or PICC line(peripherally inserted central catheter) on day 0.

CD19 CAR

Eligibility Criteria

AgeUp to 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Children and adults (age 70 years or younger) with high risk/relapsed CD19+ haematological malignancy:
  • Resistant disease (\>25% blasts) at end of UKALL 2011 or equivalent induction
  • ALL with persistent high level MRD at 2nd time point of frontline national protocol (currently \> 5 x 10-3 at week 14 UKALL2011 or equivalent)
  • High risk infant ALL (age \< 6 months at diagnosis with MLL gene rearrangement and either presenting white cell count \> 300 x 109/L or poor steroid early response (i.e circulating blast count \>1x109/L following 7 day steroid pre- phase of Interfant 06)
  • Intermediate risk infant ALL with MRD \> 10-3 at end of Interfant06 induction
  • Very early (\< 18 months from diagnosis) bone marrow or extramedullary relapse of acute lymphoblastic leukaemia (ALL)
  • Early (within 6 months of finishing therapy) bone marrow, or combined extramedullary relapse of ALL with bone marrow minimal residual disease (MRD) \> 10-3 at end of re-induction
  • Any on therapy relapse of ALL in patients age 16-70
  • Any relapse of infant ALL
  • ALL post ≥ 2nd relapse
  • Any refractory relapse of ALL
  • ALL with MRD \>10-4 prior to planned stem cell transplant
  • Any relapse of ALL eligible for stem cell transplant but no available HLA matched donor or other contraindication to transplant
  • Any relapse of ALL after stem cell transplant
  • Any relapse of Burkitt's or other CD19+ lymphoma
  • +2 more criteria

You may not qualify if:

  • CD19 negative disease
  • Active hepatitis B, C or HIV infection
  • Oxygen saturation ≤ 90% on air
  • Bilirubin \> 3 x upper limit of normal
  • Creatinine \> 3 x upper limit of normal
  • Women who are pregnant or lactating
  • Stem Cell Transplant patients only: active acute graft-versus-host disease (GVHD) overall Grade ≥ II (Seattle criteria) or moderate/severe chronic GVHD (NIH consensus criteria) requiring systemic steroids
  • Inability to tolerate leucapheresis
  • Karnofsky (age ≥ 10 years) or Lansky (age \< 10) score ≤ 50%
  • Severe intercurrent infection at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion
  • Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion
  • Allogeneic transplant recipients with active acute GVHD overall grade \>2 or moderate/severe chronic GVHD requiring systemic steroids at the time of scheduled CD19 CAR and PD-1 Knockout Engineered T Cells infusion

Contact the study team to confirm eligibility.

Sponsors & Collaborators

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaBurkitt Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphoma, Non-HodgkinLymphoma

Central Study Contacts

Xiaoyun Shang, Dr.

CONTACT

+8618580607020shangxiaoyun@gmail.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

July 24, 2017

First Posted

October 2, 2017

Study Start

November 1, 2017

Primary Completion

October 1, 2020

Study Completion

October 1, 2022

Last Updated

October 2, 2017

Record last verified: 2017-09