Precursor B Cell Acute Lymphoblastic Leukemia (B-ALL) Treated With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19

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Brief Title

Precursor B Cell Acute Lymphoblastic Leukemia (B-ALL) Treated With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19

Official Title

A Phase I Trial of Precursor B Cell Acute Lymphoblastic Leukemia (B-ALL) Treated With Autologous T Cells Genetically Targeted to the B Cell Specific Antigen CD19

Brief Summary

      This study is an investigational approach that uses immune cells, called "T cells", to kill
      leukemia. These T cells are removed from blood, modified in a laboratory, and then put back
      in the body. T cells fight infections and can also kill cancer cells in some cases. However,
      right now T cells are unable to kill the cancer cells. For this reason we will put one gene
      into the T cells that allows them to recognize and kill the leukemia cells. This gene will be
      put in the T cells by a weakened virus. The gene will produce proteins in the T cells that
      help the T cells recognize the leukemia cells and possibly kill them. The doctors have found
      that T cells modified in this way can cure an ALL-like cancer in mice.

      The main goals of this study is to determine the safety and appropriate dose of these
      modified T cells in patients with ALL. This will be done in a "clinical trial." The dose of
      modified T-cells will depend on if you have disease present in your bone marrow or not. The
      patient will also receive chemotherapy before the T cells. We will use normally chemotherapy
      that is used in patients with leukemia. The chemotherapy is given to reduce leukemia and to
      allow the T cells to live longer.
    


Study Phase

Phase 1

Study Type

Interventional


Primary Outcome

To evaluate the safety of adoptive transfer of gene-modified autologous CD19-specific T cells in adult patients with B-ALL.

Secondary Outcome

 To assess the anti-leukemic effect of adoptively transferred anti-CD19 T cells.

Condition

Leukemia

Intervention

gene-modified T cells targeted

Study Arms / Comparison Groups

 Pts with B Cell Acute Lymphoblastic Leukemia
Description:  This is a phase I study. Patients with CD19+ ALL (CR, relapsed, MRD, or refractory) are eligible for enrollment. B-ALL patients in first CR will be enrolled but only treated if they develop MRD or a frank relapse, while patients with MRD or with documented relapsed/refractory disease are eligible for immediate treatment. The T cell doses originally proposed in this study were based on doses administered safely in prior autologous T cell adoptive therapy trials but the dose has been modified based on the toxicities observed in patients with morphologic evidence of disease. Patients will be treated with different doses of T cells depending on the amount of disease at the time of T cell infusion. Patients in Cohort 1 (<5% blasts in the BM) will continue to receive 10^6 19-28z+ T cells/kg as previously. Patients in Cohort 2 (≥5% blasts in the BM) will receive the reduced dose of 1x106 19-28z+ T cells/kg).

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

93

Start Date

January 5, 2010

Completion Date

January 2021

Primary Completion Date

January 2021

Eligibility Criteria

        Inclusion Criteria:

          -  Adult patients are eligible (> or = to 18 year old).

          -  Patients must have B- ALL refractory, relapsed, MRD, or in first CR as described
             below.

          -  Complete remission is defined as restoration of normal hematopoiesis with a neutrophil
             count > 1,000 x 106/L, a platelet count > 100,000 x 106/L, and hemoglobin > 10 g/dL.
             Blasts should be < 5% in a post-treatment bone marrow differential. Furthermore, there
             should be no clinical evidence of leukemia for a minimum of four weeks.

          -  MRD is defined as patients meeting the criteria for CR above, but with residual
             disease measured by a quantitative PCR, or by flow or by deep-sequencing of the IgH
             rearrangements . The assay from blood and/or bone marrow defines MRD by qPCR as a
             cycle threshold (CT) that is at least 1 CT value < than the lowest CT value from the
             background. Outside laboratory tests may suffice for this assessment at the discretion
             of the Principal Investigator.

        Relapsed B-ALL will be defined as patients that meet the above criteria for a CR before
        developing recurrent disease (increased bone marrow blasts). Refractory patients will be
        defined as patients that have not achieved a CR after 1 cycle of induction chemotherapy

          -  Patients must have a diagnosis of B-ALL by flow cytometry, or bone marrow histology,
             and/or cytogenetics.

          -  Patients must have CD19+ ALL as confirmed by flow cytometry and/or
             immunohistochemistry.

          -  Creatinine < 2.0 mg/100 ml, bilirubin < 2.0 mg/100 ml, AST and ALT < 3x normal, PT and
             PTT < 2x normal outside the setting of stable chronic anticoagulation therapy. LFTs
             (Bilirubin, AST, and/or ALT) may be acceptable if the elevation is secondary to
             leukemia infiltration or leukemia therapy with tyrosine kinase inhibitors.

          -  Adequate cardiac function (LVEF ≥ 40%) as assessed by ECHO or MUGA or other similar
             cardiac imaging performed within 1 month of enrollment.

          -  Adequate pulmonary function as assessed by ≥ 92% oxygen saturation on room air by
             pulse oximetry.

          -  Patients must have adequate access for leukapheresis procedure as assessed by staff
             from the MSKCC Donor Room.

          -  Life expectancy > 3 months

        Exclusion Criteria:

          -  Karnofsky performance status < 70.

          -  Active central nervous system (CNS) leukemia, as defined by unequivocal morphologic
             evidence of lymphoblasts in the cerebrospinal fluid (CSF) or symptomatic CNS leukemia
             (i.e. cranial nerve palsies or other significant neurologic dysfunction) within 28
             days of enrollment. Prophylactic intrathecal medication is not a reason for exclusion.

          -  Patients previously treated with an allogeneic SCT that is currently complicated by
             active GVHD requiring T cell suppressive therapy.

        Patients with following cardiac conditions will be excluded:

          -  New York Heart Association (NYHA) stage III or IV congestive heart failure

          -  Myocardial infarction ≤6 months prior to enrollment

          -  History of clinically significant ventricular arrhythmia or unexplained syncope, not
             believed to be vasovagal in nature or due to dehydration

          -  History of severe non-ischemic cardiomyopathy with EF ≤20%

               -  Patients with HIV, hepatitis B or hepatitis C infection.

               -  Patients with any concurrent active malignancies as defined by malignancies
                  requiring any therapy other than expectant observation.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Jae Park, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01044069

Organization ID

09-114


Responsible Party

Sponsor

Study Sponsor

Memorial Sloan Kettering Cancer Center


Study Sponsor

Jae Park, MD, Principal Investigator, Memorial Sloan Kettering Cancer Center


Verification Date

February 2020