NCT02685670

Brief Summary

This is a single-arm open-label phase I/II study to determine the relative superiority of αCD19-TCRζ-CD28 and αCD19-TCRζ-CD137 CAR-T Cells in safety, efficacy and engraftment potential in patients with CD19+ B-lineage leukemia and lymphoma. Recently, cancer immunotherapy, treatments aiming to arm patients with immunity specifically against cancer cells, has emerged as a promising therapeutic strategy. Clinical trials utilizing CARs against B cell malignancies have demonstrated remarkable potential. In this trial, all subjects will be competitively infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number to test a hypothesis that CD137-costimulation can promote the persistence and engraftment of CAR-T cells and this superiority can lead to improved progression-free survival.

Trial Health

43
At Risk

Trial Health Score

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

Trial has exceeded expected completion date
Enrollment
20

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Feb 2016

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
unknown

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2016

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

February 14, 2016

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 19, 2016

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2017

Completed
2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
Last Updated

March 16, 2017

Status Verified

March 1, 2017

Enrollment Period

1.8 years

First QC Date

February 14, 2016

Last Update Submit

March 14, 2017

Conditions

Outcome Measures

Primary Outcomes (1)

  • Safety (incidence of adverse events defined as dose-limited toxicity)

    30 days

Secondary Outcomes (4)

  • Overall complete remission rate

    8 weeks

  • Survival of CAR T cells in circulation measured by flow cytometry and PCR

    1 year

  • Duration of remission

    1 year

  • Overall survival

    1 year

Study Arms (1)

Mixed CD19CAR transfer

EXPERIMENTAL

All subjects will be infused with αCD19-TCRz-CD28 and αCD19-TCRz-CD137 CAR-T cells in equal number

Biological: anti-CD19 CAR-TDrug: FludarabineDrug: Cyclophosphamide

Interventions

anti-CD19 CAR-TBIOLOGICAL

Ex vivo-expanded autologous T cells modified to express CD19 CAR

Mixed CD19CAR transfer
Mixed CD19CAR transfer
Mixed CD19CAR transfer

Eligibility Criteria

Age5 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Years to 70 Years, Male and female;
  • Expected survival \> 12 weeks;
  • Performance score 0-2;
  • Histologically confirmed as CD19-positive lymphoma/leukemia and who meet one of the following conditions;
  • Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
  • Disease recurrence after stem cell transplantation;
  • Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy
  • Creatinine \< 2.5 mg/dl;
  • ALT/AST \< 3x normal;
  • Bilirubin \< 2.0 mg/dl;
  • Adequate venous access for apheresis, and no other contraindications for leukapheresis;
  • Take contraceptive measures before recruit to this trial;
  • Written voluntary informed consent is given.

You may not qualify if:

  • Patients with symptoms of central nervous system
  • Accompanied by other malignant tumor
  • Active hepatitis B or C, HIV infection
  • Any other diseases could affect the outcome of this trial
  • Suffering severe cardiovascular or respiratory disease
  • Poorly controlled hypertension
  • A history of mental illness and poorly controlled
  • Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
  • Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
  • Reaching a steady dose if receiving anticoagulant therapy before assignment
  • Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
  • Pregnant or lactating women
  • Subject suffering disease affects the understanding of informed consent or comply with study protocol.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Henan Province of TCM

Zhengzhou, Henan, China

RECRUITING

MeSH Terms

Conditions

Hematologic NeoplasmsLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Large B-Cell, DiffuseLymphoma, FollicularLymphoma, Mantle-Cell

Interventions

fludarabineCyclophosphamide

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLeukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphoma, B-CellLymphoma, Non-HodgkinLymphoma

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Zhi Cheng, M.D.

    The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Director of Department of Hematology

Study Record Dates

First Submitted

February 14, 2016

First Posted

February 19, 2016

Study Start

February 1, 2016

Primary Completion

December 1, 2017

Study Completion

December 1, 2019

Last Updated

March 16, 2017

Record last verified: 2017-03

Locations