NCT03919526

Brief Summary

To evaluate the safety and efficacy of CD19/CD22 Bispecific chimeric antigen receptor (CAR)-T for the treatment of measurable residual disaese (MRD)-positive B cell acute lymphoblastic leukemia. Patients will be given a conditioning chemotherapy regimen of fludarabine and cyclophosphamide followed by a single infusion of CD19/CD22 CAR+ T cells.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Aug 2019

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

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

First Submitted

Initial submission to the registry

April 7, 2019

Completed
11 days until next milestone

First Posted

Study publicly available on registry

April 18, 2019

Completed
4 months until next milestone

Study Start

First participant enrolled

August 11, 2019

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2023

Completed
Last Updated

December 8, 2023

Status Verified

December 1, 2023

Enrollment Period

4.2 years

First QC Date

April 7, 2019

Last Update Submit

December 3, 2023

Conditions

MRD-positiveAcute Lymphoblastic Leukemia

Keywords

CD19/CD22Bispecific CAR-TleukemiaMRD-positiveB-ALL

Outcome Measures

Primary Outcomes (1)

  • Safety measured by occurence of study related adverse effects defined by NCI CTCAE5.0

    Safety measured by occurence of study related adverse effects defined by NCI CTCAE5.0

    28 days post infusion

Secondary Outcomes (6)

  • MRD clearance

    3 months post infusion

  • Content of CD19 positive B-cells in peripheral blood

    3 months post infusion

  • Content of CAR-T related cytokines positive T cells in circulation

    3 months post infusion

  • Total response rate (ORR) after administration

    3 months post infusion

  • Duration of remission (DOR) after administration

    2 years post infusion

  • +1 more secondary outcomes

Study Arms (1)

anti-CD19/CD22 CAR-T cells

EXPERIMENTAL

Administration with anti-CD19/ CD22 CAR-T cells in the MRD-positive ALL patients.

Biological: anti-CD19/CD22 CAR-T cellsDrug: FludarabineDrug: Cyclophosphamide

Interventions

anti-CD19/CD22 CAR-T cellsBIOLOGICAL

Retroviral vector-transduced autologous T cells to express anti-CD19 and anti-CD22 CARs

anti-CD19/CD22 CAR-T cells
FludarabineDRUG

30mg/m2/d

anti-CD19/CD22 CAR-T cells
CyclophosphamideDRUG

300mg/m2/d

anti-CD19/CD22 CAR-T cells

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • (1) CD19 positive/CD22 positive, or CD19-CD22 positive B-cell acute lymphoblastic leukemia;
  • (2)18 to 70 Years Old, Male and female;
  • (3) Expected survival \> 12 weeks;
  • (4) ECOG score 0-2;
  • (5) Bone marrow examination clearly diagnosed as B-cell acute lymphoblastic leukemia and who met one of the following conditions:
  • Recurrent patients who achieves MRD-positive CR or CRi after standard therapy;
  • Those who achieves CR, but failed to achieve MRD-negative after at least 2 courses of consolidation therapy;
  • For Ph-positive ALL patients, a history of at least one TKI application is required in addition to two standard chemotherapy treatments
  • (6) The venous access required for collection can be established and mononuclear cell collection can be determined by the investigators;
  • (7) Liver, kidney and cardiopulmonary functions meet the following requirements:
  • Creatinine is in the normal range;
  • Left ventricular ejection fraction \>50%;
  • Baseline oxygen saturation\>92%;
  • Total bilirubin ≤ 2×ULN;
  • ALT and AST ≤ 2.5×ULN;
  • +1 more criteria

You may not qualify if:

  • (1) Malignant tumors other than acute lymphoblastic leukemia within 5 years prior to screening, in addition to adequately treated cervical carcinoma in situ, basal cell or squamous cell skin cancer, localized prostate cancer after radical resection, and ductal carcinoma in situ after radical resection;
  • (2) Subjects with positive HBsAg or HBcAb and peripheral blood HBV DNA titer detection ≥ 1 × 102 copy number / L; HCV antibody positive and peripheral blood HCV RNA positive; HIV antibody positive; CMV DNA positive; syphilis positive;
  • (3) Any instability of systemic disease, including but not limited to unstable angina, cerebrovascular accident, or transient cerebral ischemic (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), congestive heart failure (New York heart association (NYHA) classification ≥ III), need drug therapy of severe arrhythmia, liver, kidney, or metabolic disease;
  • (4) Active or uncontrollable infection requiring systemic therapy within 14 days prior to enrollment;
  • (5) Pregnant or lactating woman, and female subject who plans to have a pregnancy within 1 year after cell transfusion, or male subject whose partner plans to have a pregnancy within 1 year after cell transfusion;
  • (6) Received CAR-T treatment or other gene therapies before enrollment;
  • (7) Patients with symptoms of central nervous system;
  • (8) Subjects who are receiving systemic steroid treatment and requiring long-term systemic steroid treatment during the treatment as determined by the investigator before screening (except inhalation or topical use); And subjects treated with systemic steroids (except inhalation or topical use) within 72h prior to cell transfusion;
  • (9) The investigators consider other conditions unsuitable for enrollment.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-LymphomaLeukemia

Interventions

fludarabineCyclophosphamide

Condition Hierarchy (Ancestors)

Leukemia, LymphoidNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Xianmin Song, M.D.

    Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

    PRINCIPAL INVESTIGATOR

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
principal investigator

Study Record Dates

First Submitted

April 7, 2019

First Posted

April 18, 2019

Study Start

August 11, 2019

Primary Completion

November 1, 2023

Study Completion

November 1, 2023

Last Updated

December 8, 2023

Record last verified: 2023-12

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)