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Modified Immune Cells (CD19-CD22 CAR T Cells) in Treating Patients With Recurrent or Refractory CD19 Positive, CD22 Positive Leukemia or Lymphoma

NCT04029038

Description:

This phase I/II trial studies the side effects and best dose of modified immune cells called CD19-CD22 chimeric antigen receptor (CAR) T cells in treating patients with CD19 positive(+), CD22+ B-acute lymphoblastic leukemia, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma that has come back (recurrent) or does not respond to treatment (refractory). T-cells are collected from the patient and genetic materials called "chimeric antigen receptors (CAR)" are transferred to the collected T-cells. The CAR T-cells are then infused back to the patient's body. Giving CD19- CD22 CAR T cells after chemotherapy may help to control the disease.

Related Conditions:
  • B-Cell Acute Lymphoblastic Leukemia
  • Chronic Lymphocytic Leukemia
  • Non-Hodgkin Lymphoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Modified Immune Cells (CD19-CD22 CAR T Cells) in Treating Patients With Recurrent or Refractory CD19 Positive, CD22 Positive Leukemia or Lymphoma
  • Official Title: Phase I/II Study of Dual CD19-CD22 Chimeric Antigen Receptor (CAR) T Cells in Patients With Advanced CD19+ CD22+ Lymphoid Malignancies

Clinical Trial IDs

  • ORG STUDY ID: 2019-0042
  • SECONDARY ID: NCI-2019-04229
  • SECONDARY ID: 2019-0042
  • SECONDARY ID: P30CA016672
  • NCT ID: NCT04029038

Conditions

  • CD19 Positive
  • CD22 Positive
  • Minimal Residual Disease
  • Progressive Disease
  • Recurrent B Acute Lymphoblastic Leukemia
  • Recurrent Chronic Lymphocytic Leukemia
  • Recurrent Non-Hodgkin Lymphoma
  • Refractory B Acute Lymphoblastic Leukemia
  • Refractory Chronic Lymphocytic Leukemia
  • Refractory Non-Hodgkin Lymphoma

Interventions

DrugSynonymsArms
Autologous CD19/CD22 Chimeric Antigen Receptor T-cellsAutologous Anti-CD19/CD22 CAR-T Cells, Autologous CD19/CD22 CAR T Cells, Autologous CD19/CD22 CAR T-cells, Autologous CD19/CD22 Chimeric Antigen Receptor T CellsTreatment (CD19-CD22 CAR T cells)
Cyclophosphamide(-)-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, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Treatment (CD19-CD22 CAR T cells)
FludarabineFluradosaTreatment (CD19-CD22 CAR T cells)

Purpose

This phase I/II trial studies the side effects and best dose of modified immune cells called CD19-CD22 chimeric antigen receptor (CAR) T cells in treating patients with CD19 positive(+), CD22+ B-acute lymphoblastic leukemia, chronic lymphocytic leukemia, or non-Hodgkin's lymphoma that has come back (recurrent) or does not respond to treatment (refractory). T-cells are collected from the patient and genetic materials called "chimeric antigen receptors (CAR)" are transferred to the collected T-cells. The CAR T-cells are then infused back to the patient's body. Giving CD19- CD22 CAR T cells after chemotherapy may help to control the disease.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine the safety of infusion with chimeric antigen receptor T cells targeting CD19
      and CD22.

      II. To find the recommended phase II dose for recurrent/refractory CD19+CD22+ B cell
      malignancies.

      SECONDARY OBJECTIVES:

      I. To describe the overall response rate and complete response rate of relapsed B cell
      malignancies treated with CAR-T cells targeting CD19 and CD22.

      II. To assess other response variables including minimal residual disease (MRD) negative
      remission, overall survival (OS), and event free survival (EFS).

      EXPLORATORY OBJECTIVES:

      I. To evaluate the immune reconstitution and persistence of CAR T cells for one year post
      infusion.

      OUTLINE: This is a phase I, dose escalation study of autologous CD19/CD22 chimeric antigen
      receptor T-cells (CD19-CD22 CAR T cells) followed by a phase II study.

      Patients receive standard of care cyclophosphamide intravenously (IV) over 30 minutes and
      fludarabine IV over 30 minutes on days -5, -4, and -3, and then receive CD19-CD22 CAR T cells
      IV on day 0. Patients with relapsed or persistent disease after a protocol assessment may
      receive a second infusion of CD19-CD22 CAR T cells.

      After completion of study treatment, patients are followed up at 1, 2, 3, 6, and 12 months.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (CD19-CD22 CAR T cells)ExperimentalPatients receive standard of care cyclophosphamide IV over 30 minutes and fludarabine IV over 30 minutes on days -5, -4, and -3, and then receive CD19-CD22 CAR T cells IV on day 0. Patients with relapsed or persistent disease after a protocol assessment may receive a second infusion of CD19-CD22 CAR T cells.
  • Autologous CD19/CD22 Chimeric Antigen Receptor T-cells
  • Cyclophosphamide
  • Fludarabine

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with relapsed/refractory B-acute lymphoblastic leukemia (ALL), chronic
             lymphocytic leukemia (CLL), or non-Hodgkin's lymphoma (NHL) treated with at least two
             lines of therapy, and have persistent or progressed disease including positive minimal
             residual disease (MRD)

          -  Patients may have received last cytotoxic chemotherapy at least 3 weeks prior to
             lymphodepleting chemotherapy

          -  Patient may continue targeted therapy until 2 weeks before initiation of
             lymphodepleting chemotherapy with the exception of ibrutinib

          -  Disease must be CD19 and/or CD22 positive by flow cytometry or immunohistochemistry

          -  Karnofsky/Lansky performance scale > 70

          -  Total bilirubin less than < 1.5 mg/dL except patients with Gilbert syndrome whose
             total bilirubin must be < 3.0mg/dL

          -  Aspartate aminotransferase (AST)(serum glutamic-oxaloacetic transaminase [SGOT]) =<
             2.5 X upper limit of normal (ULN)

          -  Alanine aminotransferase (ALT)(serum glutamate pyruvate transaminase [SGPT]) =< 5.0
             ULN

          -  Serum creatinine (as estimated by Cockcroft Gault) >= 60 cc/min

          -  Cardiac ejection fraction >= 50% without evidence of pericardiac effusion as
             determined by echocardiogram (ECHO) or multigated acquisition scan (MUGA), no clinical
             significant electrocardiogram (ECG) findings

          -  No clinical significant pleural effusion and baseline oxygen saturation >= 92%

          -  Absolute lymphocyte count >= 100/ul

          -  Be able to sign informed consent

          -  All participants who are able to have children must practice effective birth control
             while on study. Acceptable forms of birth control for female patients include: birth
             control pills, patches, or injections, intrauterine device (IUD), diaphragm with
             spermicide, or condom with spermicide. Acceptable forms of birth control for male
             patients include condom with spermicide. If female participant becomes pregnant during
             the study, she will be taken off this study. If male participant fathers a child while
             on study, he must immediately notify his doctor

          -  For patients with history of allogenic stem cell transplantation

               -  Should not have active acute graft-versus-host disease (GVHD) grade >= 2

               -  Should not be on immunosuppressants such as tacrolimus, sirolimus, cyclosporine,
                  mycophenolates for a minimum of a month from CD19-CD22 CAR T cell infusion

               -  Should not be on more than physiologic dose of systemic steroid for adrenal
                  insufficiency (prednisone equivalent 5mg/day)

               -  Transplantation should be more than 2 months from CD19-CD22 CAR T cell infusion

               -  Other cell therapy including CAR T cells, donor lymphocyte infusion, virus
                  specific T cells, natural killer (NK) cells, etc should have 6 weeks of wash-out
                  period from the CD19-CD22 CAR T cell infusion

          -  For patients with history of central nervous system (CNS) disease, CNS disease must be
             treated prior to enrollment

          -  For patients with prior treatment history of cell therapy such as other CAR T cells or
             CAR NK cells or NK cells, cell therapy should have a 6 weeks of wash-out period from
             CD19-CD22 CAR T cell infusion

          -  Be able to consent long-term follow-up protocol PA17-0483

        Exclusion Criteria:

          -  Positive beta-human chorionic gonadotropin (hCG) in female of child bearing potential
             defined as not postmenopausal for 24 months or no previous surgical sterilization or
             lactating females

          -  Known positive serology for human immunodeficiency virus (HIV)

          -  Presence of active grade 3 or greater toxicity from the previous treatment

          -  Presence of active fungal, bacterial, viral, or other infection requiring IV
             antibiotics for management

          -  Presence of active neurologic disorders

          -  Concomitant use of other investigational agents

          -  Current use of corticosteroid more than physiological dose for adrenal insufficiency
             (prednisone equivalent at a dose higher than 10 mg/day)

          -  Presence of active CNS disease
      
Maximum Eligible Age:70 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Optimal chimeric antigen receptor (CAR) T cell dose level
Time Frame:Up to 30 days
Safety Issue:
Description:Dose-finding will be done using the sequentially adaptive phase I-II EffTox method.

Secondary Outcome Measures

Measure:Progression-free survival
Time Frame:Up to 1 year post T-cell infusion
Safety Issue:
Description:Unadjusted distributions of the time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and T-cell dose level will be evaluated by Bayesian piecewise exponential survival regression.
Measure:Overall survival
Time Frame:Up to 1 year post T-cell infusion
Safety Issue:
Description:Unadjusted distributions of the time-to-event outcomes will be estimated using the method of Kaplan and Meier and their relationship to prognostic covariates and T-cell dose level will be evaluated by Bayesian piecewise exponential survival regression.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

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