CD19 CAR T Cells for B Cell Malignancies After Allogeneic Transplant

NCT01475058 | Completed Phase 1 DMC

• 4 other identifiers: 2494.00NCI-2011-01819P30CA015704R01CA136551
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• Safety and toxicity assessment of study treatment

  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.

  Up to day 42 after the T cell infusion

• Feasibility assessment of study treatment

  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.

  Up to 5 years

Secondary Outcomes (1)

• Anti-tumor efficacy and duration of persistence, migration, and function of adoptively transferred bi-specific effector cells

  Up to 15 years

Study Arms (1)

Treatment (T cell therapy)

EXPERIMENTAL

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.

Biological: allogeneic cytomegalovirus-specific cytotoxic T lymphocytes

Interventions

allogeneic cytomegalovirus-specific cytotoxic T lymphocytes BIOLOGICAL

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

Also known as: allogeneic CMV-specific CTLs

Treatment (T cell therapy)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• 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.

  PMID: 34515338 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Leukemia, B-Cell; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Cameron Turtle

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 10, 2011
• First Posted: November 21, 2011
• Study Start: April 1, 2012
• Primary Completion: April 1, 2014
• Study Completion: July 1, 2014
• Last Updated: February 15, 2017

Record last verified: 2017-02

Locations

US (1)