NCT03579888

Brief Summary

This phase I trial investigates the side effects and best dose of CD19 positive (+) specific CAR-T cells in treating patients with CD19+ lymphoid malignancies, such as acute lymphoblastic leukemia, non-Hodgkin lymphoma, small lymphocytic lymphoma, or chronic lymphocytic lymphoma. Sometimes researchers change the genetic material in the cells of a patient's T cells using a process called gene transfer. Researchers then inject the changed T-cells into the patient's body. Receiving the T-cell infusion may help to control the disease.

Trial Health

57
Monitor

Trial Health Score

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

Enrollment
4

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Jun 2020

Geographic Reach
1 country

1 active site

Status
terminated

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

June 25, 2018

Completed
14 days until next milestone

First Posted

Study publicly available on registry

July 9, 2018

Completed
2 years until next milestone

Study Start

First participant enrolled

June 26, 2020

Completed
11 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 27, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 27, 2021

Completed
Last Updated

June 2, 2021

Status Verified

May 1, 2021

Enrollment Period

11 months

First QC Date

June 25, 2018

Last Update Submit

May 28, 2021

Conditions

B Acute Lymphoblastic Leukemia With t(v;11q23.3); KMT2A RearrangedRecurrent B Acute Lymphoblastic LeukemiaRecurrent Chronic Lymphocytic LeukemiaRecurrent Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent Mantle Cell LymphomaRecurrent Non-Hodgkin LymphomaRecurrent Ph-Like Acute Lymphoblastic LeukemiaRecurrent Primary Mediastinal (Thymic) Large B-Cell Cell LymphomaRecurrent Small Lymphocytic LymphomaRefractory B Acute Lymphoblastic LeukemiaRefractory Chronic Lymphocytic LeukemiaRefractory Diffuse Large B-Cell Lymphoma, Not Otherwise SpecifiedRefractory Mantle Cell LymphomaRefractory Non-Hodgkin LymphomaRefractory Ph-Like Acute Lymphoblastic LeukemiaRefractory Primary Mediastinal (Thymic) Large B-Cell Cell LymphomaRefractory Small Lymphocytic Lymphoma

Outcome Measures

Primary Outcomes (2)

  • Incidence of adverse events

    Graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Adverse events will be summarized by frequencies and percentages by dose level.

    Up to 15 years

  • Maximum tolerated dose (MTD) as determined by dose limiting toxicity (DLT)

    The MTD is defined as the highest dose at which no more than 1 of 6 patients experiences a DLT. The study will employ a standard 3+3 design to find the MTD of CD19-specific chimeric antigen receptor (CAR) T cell dose.

    Up to 30 days post-infusion

Secondary Outcomes (11)

  • Incidence and grading of cytokine release syndrome (CRS)

    Up to 12 months

  • Persistence of genetically modified T cells

    Up to 12 months

  • Change in numbers of infused T cells

    Up to 12 months

  • Development of host immune responses against transgenes

    Up to 12 months

  • Cytokine levels

    Up to 12 months

  • +6 more secondary outcomes

Study Arms (1)

Treatment (fludarabine, cyclophosphamide, CD19 T cell)

EXPERIMENTAL

CHEMOTHERAPY: Patients receive fludarabine IV over 1 hour and cyclophosphamide IV over 3 hours on days -5, -4, and -3 in the absence of disease progression or unacceptable toxicity. T-CELL INFUSION: Patients receive autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T cells IV over 15-30 minutes on day 0.

Biological: Autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T CellsDrug: CyclophosphamideDrug: Fludarabine

Interventions

Autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-HER1t T CellsBIOLOGICAL

Given IV

Also known as: Autologous CD19-CD8-CD28-CD3zeta-CAR-mbIL15-EGFRt T Cells, CD19-CD8CD28zCAR-specific-mbIL15-HER1t T-lymphocytes
Treatment (fludarabine, cyclophosphamide, CD19 T cell)
CyclophosphamideDRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719
Treatment (fludarabine, cyclophosphamide, CD19 T cell)
FludarabineDRUG

Given IV

Also known as: Fluradosa
Treatment (fludarabine, cyclophosphamide, CD19 T cell)

Eligibility Criteria

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

You may qualify if:

  • RECIPIENT: Patients with high risk or relapsed disease who are planning to receive, or have received prior allogeneic HSCT from an human leukocyte antigen (HLA)-matched related, or HLA-mismatched related donor; high risk is defined as patients with acute lymphoblastic leukemia who have delayed clearance of minimal residual disease, Philadelphia (Ph)-like, or complex, 11q23 or hypodiploid karyotype
  • RECIPIENT: Available donor who provided hematopoietic stem-cell (HSC)
  • RECIPIENT: Patients with CD19+ lymphoid malignancies that are refractory to or intolerant of standard treatment (as defined below):
  • B-cell Acute Lymphoblastic Leukemia (ALL)
  • Non-Hodgkin lymphoma (NHL) to include diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B cell lymphoma, mantle cell lymphoma, or transformed follicular lymphoma (TFL) as defined by the World Health Organization 2008 criteria
  • Small lymphocytic lymphoma (SLL)
  • Chronic lymphocytic leukemia (CLL)
  • NOTE: Refractory disease for acute and chronic leukemia is defined by:
  • Presence of \> 5% malignant blasts in bone marrow and/or peripheral blood and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins and/or positive imaging for extra-medullary disease to most recent therapy
  • NOTE: Refractory disease for lymphoma is defined as:
  • Progressive disease or stable disease lasting =\< 6 months, as best response to most recent chemotherapy regimen; or disease progression or recurrence =\< 12 months after prior ASCT
  • Prior therapy must have included an anti-CD20 monoclonal antibody-containing regimen and an anthracycline-containing chemotherapy regimen
  • For patients with TFL, prior chemotherapy for follicular lymphoma and subsequent refractory disease after transformation to DLBCL
  • At least one measurable lesion according to revised International Working Group (IWG) Response Criteria
  • RECIPIENT: In patients with prior transplant, treatment will begin no earlier than 3 months post-transplant. Enrollment can occur earlier to allow time for donor cell collection
  • +23 more criteria

You may not qualify if:

  • RECIPIENT: Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females
  • RECIPIENT: Patients with allergy to mouse products or cetuximab
  • RECIPIENT: Active central nervous system (CNS) disease in patient with history of CNS malignancy
  • RECIPIENT: Positive serology for human immunodeficiency virus (HIV)
  • RECIPIENT: Active hepatitis B or active hepatitis C
  • RECIPIENT: Has received a T-cell product within 6 weeks prior to planned infusion of genetically modified T cells

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

  • Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

    PMID: 34515338DERIVED

Related Links

MeSH Terms

Conditions

Burkitt LymphomaLeukemia, Lymphocytic, Chronic, B-CellLymphoma, Large B-Cell, DiffuseLymphoma, Mantle-CellLymphoma, Non-Hodgkin

Interventions

Cyclophosphamidefludarabine

Condition Hierarchy (Ancestors)

Epstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLeukemia, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus Compounds

Study Officials

  • Partow Kebriaei

    M.D. Anderson Cancer Center

    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
SPONSOR

Study Record Dates

First Submitted

June 25, 2018

First Posted

July 9, 2018

Study Start

June 26, 2020

Primary Completion

May 27, 2021

Study Completion

May 27, 2021

Last Updated

June 2, 2021

Record last verified: 2021-05

Locations

US(1)