CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant

NCT ID: NCT01475058

Last Updated: 2017-02-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-04-30
• Study Completion Date: 2014-07-31

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 matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy.

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 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

allogeneic cytomegalovirus-specific cytotoxic T lymphocytes

Intervention Type: BIOLOGICAL

Allogeneic CD19-specific chimeric antigen receptor-modified CD8+ central memory derived virus-specific T cells. Allogeneic CD19CAR-TCM cells given IV

Interventions

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

Intervention Type: BIOLOGICAL

Other Intervention Names

allogeneic CMV-specific CTLs

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Cameron Turtle

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cameron Turtle

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

References

Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

Reference Type: DERIVED

PMID: 34515338 (View on PubMed)

Other Identifiers

NCI-2011-01819

Identifier Type: REGISTRY

Identifier Source: secondary_id

2494.00

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01CA136551

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2494.00

Identifier Type: -

Identifier Source: org_study_id