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

This study has suspended participant recruitment.
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT01044069
First received: January 6, 2010
Last updated: April 3, 2014
Last verified: April 2014
  Purpose

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 patient may be treated with one of three T cells. If too many serious side effects are seen with the one dose, additional patients may be treated with a lower dose to make sure that this dose is safe. 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.


Condition Intervention Phase
Leukemia
Acute Lymphoblastic Leukemia
Biological: gene-modified T cells targeted to B-ALL tumor cells
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Memorial Sloan-Kettering Cancer Center:

Primary Outcome Measures:
  • To evaluate the safety of adoptive transfer of gene-modified autologous CD19-specific T cells in adult patients with B-ALL. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To assess the anti-leukemic effect of adoptively transferred anti-CD19 T cells. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: January 2010
Estimated Study Completion Date: January 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pts with B Cell Acute Lymphoblastic Leukemia
This is a phase I dose escalation study. The T cell dose proposed in this study are based on doses administered safely in prior autologous T cell adoptive therapy trials72-74. 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 minimal residual disease (MRD) or a frank relapse, while patients with MRD or with documented relapsed/refractory disease are eligible for immediate treatment.
Biological: gene-modified T cells targeted to B-ALL tumor cells
Patients will undergo leukapheresis at the blood donor center at MSKCC. Peripheral T cells will be quantified by FACS to verify a sufficient number is present (> 3 x 108 CD3+ T cells). The leukapheresis product will be washed and frozen until the GTF is directed to start T cell production by the Principal Investigator. Enrolled patients must have documented MRD or relapsed or refractory disease before the treatment algorithm of this clinical protocol is initiated. Patients will be treated with a chemotherapeutic regimen, chosen by the treating physician based on prior therapy, after confirmation of disease status. After completion of chemotherapy, CD3+ T cells will be isolated from the leukapheresis product using CD3/CD28 beads in the GTF at MSKCC. Next, activated T cells will be transduced with the 19-28z chimeric receptor and expanded with CD3/CD28 magnetic beads.
Other Names:
  • All relapsed and refractory patients will be given a re-induction chemotherapy regimen (chosen by the treating physician) as an inpatient on the
  • leukemia service. Patients will be infused with T cells based on one of two
  • different infusion schemes: 1) 2 and 3 days after their last
  • chemotherapy or 2) with an initial 1/3 dose given 2 days after
  • chemotherapy and the remaining dose infused within 30 days of their last
  • chemotherapy. The decision for treating the patient with one of the above
  • schemes will be made by the treating physician and principal investigator.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients are eligible (> or = to 18 year old).
  • Patients must have 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. These studies are to be performed and/or evaluated at Memorial Hospital.
  • Patients must have CD19+ ALL as confirmed by flow cytometry.
  • 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.
  • Patients previously treated with an allogeneic SCT that is currently complicated by active GVHD requiring T cell suppressive therapy.
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01044069

Locations
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Memorial Sloan-Kettering Cancer Center
Investigators
Principal Investigator: Jae Park, MD Memorial Sloan-Kettering Cancer Center
  More Information

Additional Information:
No publications provided by Memorial Sloan-Kettering Cancer Center

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Memorial Sloan-Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT01044069     History of Changes
Other Study ID Numbers: 09-114
Study First Received: January 6, 2010
Last Updated: April 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Memorial Sloan-Kettering Cancer Center:
Cyclophosphamide
T cell
leukapheresis
stem cell transplant
bone marrow transplant
09-114

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoma, B-Cell
Neoplasms, Experimental
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014