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CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01475058
First received: November 10, 2011
Last updated: August 4, 2015
Last verified: August 2015

November 10, 2011
August 4, 2015
April 2012
April 2014   (final data collection date for primary outcome measure)
  • Safety and toxicity assessment of study treatment [ Time Frame: Up to day 42 after the T cell infusion ] [ Designated as safety issue: Yes ]
    Incidence of grade >= 3 toxicity, as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 occurring from the T cell infusion through day 42 after the T cell infusion. Analysis will be performed separately in patients in complete remission (cohort A) or with detectable disease (cohort B) at day 28 post-transplant (prior to the T cell infusion). Incidence of acute GVHD occurring from the T cell infusion through day 42 after the T cell infusion will be assessed.
  • Feasibility assessment of study treatment [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    If the prescribed T cell dose is delivered in more than 50% of the patients, this approach will be considered feasible for further study to reduce relapse after allogeneic HCT.
  • Toxicity assessment [ Time Frame: Day 42 after the final T cell infusion ] [ Designated as safety issue: Yes ]
    Incidence of grade ≥ 3 toxicity, as defined by NCI CTCAE version 4.0 occurring from the first T cell infusion through day 42 after the final T cell infusion. Analysis will be performed separately in patients in complete remission (cohort A) or with detectable disease (cohort B) at day 28 post-transplant (prior to the first T cell infusion).
  • Graft-versus-host disease (GVHD) assessment [ Time Frame: Day 42 after the final T cell infusion ] [ Designated as safety issue: Yes ]
    Incidence of acute GVHD occurring from the first T cell infusion through day 42 after the final T cell infusion
Complete list of historical versions of study NCT01475058 on ClinicalTrials.gov Archive Site
Anti-tumor efficacy and duration of persistence, migration, and function of adoptively transferred bi-specific effector cells [ Time Frame: Up to 15 years ] [ Designated as safety issue: No ]
Efficacy, defined as >25% reduction in tumor burden. [ Time Frame: One month after the final T cell infusion ] [ Designated as safety issue: No ]
The frequency of greater-than-partial response (defined as > 25% reduction in tumor burden) at one month after the final T cell infusion will be determined In patients with detectable tumor at day +28 post-transplant (prior to the first T cell infusion).
Not Provided
Not Provided
 
CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant
A Phase I/II Study of Cellular Immunotherapy With Donor Central Memory-derived Virus-specific CD8+ T-cells Engineered to Target CD19 for CD19+ Malignancies After Allogeneic Hematopoietic Stem Cell Transplant
This phase I/II trial studies the safety and toxicity of post-transplant treatment with donor T cells engineered to express a chimeric antigen receptor (CAR) targeting CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy.

PRIMARY OBJECTIVES:

I. To assess the safety and feasibility of pre-emptive adoptive T cell therapy using ex vivo expanded cytomegalovirus (CMV)- or Epstein-Barr virus (EBV)-specific T cells derived from donor CD62L+ central memory (TCM) cells and genetically modified to express a CD19-specific chimeric antigen receptor (CAR) in patients in complete remission after human leukocyte antigen (HLA)-matched related donor hematopoietic stem cell transplantation (HCT) for CD19+ B cell malignancies at high risk of post-HCT relapse. (Cohort A)

II. To assess the safety and feasibility of adoptive T cell therapy using ex vivo expanded CMV- or EBV-specific T cells derived from donor CD62L+ TCM cells and genetically modified to express a CD19-specific CAR in patients with persistent, progressive or relapsed disease after HLA-matched related donor HCT for CD19+ B cell malignancies. (Cohort B)

SECONDARY OBJECTIVES:

I. To determine the duration of in vivo persistence of adoptively transferred bi-specific CD8+ T cells, and the phenotype of persisting T cells.

II. To determine if adoptively transferred bi-specific CD8+ T cells traffic to the bone marrow and function in vivo.

III. To determine if adoptively transferred bi-specific CD8+ T cells proliferate in allogeneic HCT recipients that reactivate CMV or EBV.

IV. To determine if the adoptive transfer of bi-specific CD8+ T cells eliminates CD19+ tumor cells in the subset of patients with a measurable tumor burden prior to T cell transfer.

OUTLINE:

At least 30 days after HCT, patients will receive one intravenous (IV) infusion of CMV/CD19 or EBV/CD19 bi-specific CD8+ T cells.

After completion of study treatment, patients are followed up periodically for 15 years.

Interventional
Phase 1
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia
  • Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia
  • Recurrent Adult Acute Lymphoblastic Leukemia
  • Recurrent Adult Diffuse Large Cell Lymphoma
  • Recurrent Adult Immunoblastic Large Cell Lymphoma
  • Recurrent Mantle Cell Lymphoma
  • Refractory Chronic Lymphocytic Leukemia
Biological: allogeneic cytomegalovirus-specific cytotoxic T lymphocytes
Allogeneic CD19-specific chimeric antigen receptor-modified CD8+ central memory derived virus-specific T cells. Allogeneic CD19CAR-TCM cells given IV
Other Name: allogeneic CMV-specific CTLs
Experimental: Treatment (T cell therapy)
Patients undergo one IV infusion of donor-derived CD8+ central memory-derived CMV/CD19 or EBV/CD19 bi-specific T cells, at least 30 days after HCT.
Intervention: Biological: allogeneic cytomegalovirus-specific cytotoxic T lymphocytes
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1
Not Provided
April 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients with CD19+ B cell malignancy who have persistent, relapsed or progressive disease after hematopoietic stem cell transplant from an human leukocyte antigen (HLA)-matched related donor OR patients with CD19+ B cell malignancy who are planned for or have had a hematopoietic stem cell transplant from an HLA-matched related donor and are at risk of relapse after HCT defined by any one of the disease-specific criteria listed below:

    • Philadelphia chromosome negative acute lymphoblastic leukemia:

      • Beyond first complete remission (CR) at the time of pre-transplant evaluation
      • Required > 1 cycle of induction chemotherapy to achieve CR
      • First morphologic CR but with evidence of minimal residual disease by flow cytometry, conventional cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)
      • First CR with poor risk cytogenetics (t(4:11), t(8;14), hypodiploidy, near triploidy or > 5 cytogenetic abnormalities) at diagnosis
      • Planned for or have had a reduced intensity conditioned or non-myeloablative transplant
    • Philadelphia positive acute lymphoblastic leukemia

      • Not in CR at the time of pre-transplant evaluation
      • In CR with the following features:

        • Intolerant or unwilling to use a TKI after HCT
        • Current or previous detection of cytogenetic abnormalities in addition to t(9;22) by conventional karyotyping, FISH or molecular methods
    • Chronic lymphocytic leukemia, or low grade B cell lymphomas:

      • Failed or ineligible for prior immunochemotherapy that included a purine analog and anti-CD20 monoclonal antibody AND a lymph node >= 5 cm at the time of pre-transplant evaluation
    • Mantle cell lymphoma:

      • Failed or ineligible for autologous transplant AND a lymph node >= 2 cm at the time of pre-transplant evaluation
    • Diffuse large B cell lymphomas, large B cell transformation of an indolent lymphoma or other aggressive B cell lymphomas

      • Failed or ineligible for autologous transplant AND not in CR at the time of pre-transplant evaluation
  • Confirmation of tumor diagnosis and expression of CD19 after review by University of Washington Medical Center (UWMC) or Seattle Cancer Care Alliance (SCCA) pathology services
  • The patient has signed the informed consent form for this study
  • DONOR: Genotypic or phenotypic HLA-identical family members
  • DONOR: Express one or more of the following combinations of viral serostatus and HLA allele:

    • CMV seropositive and HLA-A*0101 positive
    • CMV seropositive and HLA-A*0201 positive
    • CMV seropositive and HLA-B*0702 positive
    • CMV seropositive and HLA-B*0801 positive
    • EBV seropositive and HLA-A*0201 positive
    • EBV seropositive and HLA-B*0801 positive
  • DONOR: Hematocrit >= 35% at enrollment
  • DONOR: Age >= 18 years
  • DONOR: The donor has signed the informed consent form for the study

Exclusion Criteria:

  • Known central nervous system (CNS) tumor (CNS2 or CNS3) that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that has been effectively treated to CNS1 or lower evidence of disease will be eligible
  • Human immunodeficiency virus (HIV) seropositive
  • Significant medical or psychological conditions that would make them unsuitable candidates for T cell therapy
  • Fertile patients unwilling to use contraception during and for 12 months after protocol enrollment
  • Pregnant or breast-feeding
  • DONOR: G-CSF administered within one month prior to the blood draw for T cell collection
  • DONOR: Unable for any reason to provide a 400 ml blood draw
  • DONOR: Inadequate peripheral veins for blood collection
  • DONOR: HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1 or HTLV-2 seropositive
  • DONOR: Active hepatitis B or hepatitis C virus infection
  • DONOR: Positive serologic test for syphilis
  • DONOR: Aberrant CD45RA isoform expression on all T cells
  • DONOR: Systolic blood pressure (BP) < 80 or > 200
  • DONOR: Heart rate < 50 or > 120, if considered due to cardiac disease
  • DONOR: Oxygen (O2) saturation < 88% on room air
  • DONOR: Serum creatinine (Cr) > 3.0
  • DONOR: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 4 x the upper limit of normal
  • DONOR: Unable to provide informed consent to participate
  • DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make them unsuitable T cell donors
  • DONOR: Pregnant or nursing
Both
18 Years to 75 Years   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01475058
2494.00, NCI-2011-01819, 2494.00, P30CA015704, R01CA136551
Yes
Not Provided
Not Provided
Fred Hutchinson Cancer Research Center
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Principal Investigator: Cameron Turtle Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Fred Hutchinson Cancer Research Center
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP