Status:
COMPLETED
CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant
Lead Sponsor:
Fred Hutchinson Cancer Center
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia
Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia
Eligibility:
All Genders
18-75 years
Phase:
PHASE1
PHASE2
Brief Summary
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 ...
Detailed Description
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 f...
Eligibility Criteria
Inclusion
- 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
- 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
Key Trial Info
Start Date :
April 1 2012
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 1 2014
Estimated Enrollment :
1 Patients enrolled
Trial Details
Trial ID
NCT01475058
Start Date
April 1 2012
End Date
July 1 2014
Last Update
February 15 2017
Active Locations (1)
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1
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109