CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant

This study is currently recruiting participants.
Verified March 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01475058
First received: November 10, 2011
Last updated: March 17, 2014
Last verified: March 2014

November 10, 2011
March 17, 2014
April 2012
February 2017   (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.
 
Recruiting
30
Not Provided
February 2017   (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
No
Not Provided
United States
 
NCT01475058
2494.00, NCI-2011-01819, 2494.00, P30CA015704, R01CA136551
Yes
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
March 2014

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