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CD19.CAR T Cells in Treating Participants with CD19 Positive Malignancies after Stem Cell Transplant

Trial Status: Active

This phase I trial studies the side effects and best dose of CD19.CAR T cells in treating participants with CD19 positive malignancies after stem cell transplant. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. T lymphocytes, such as CD19.CAR T cells, may kill tumor cells but there normally are not enough of them to kill all the tumor cells.

Inclusion Criteria

  • PROCUREMENT CRITERIA
  • Group A: CD19+ B-acute lymphoblastic leukemia (ALL) undergoing allogeneic HSCT or
  • Group B: CD19+ B cell chronic lymphocytic leukemia (CLL) or non-Hodgkin lymphoma (NHL) undergoing allogeneic HSCT
  • Life expectancy of ≥ 12 weeks
  • Patient has an appropriate donor identified for hematopoietic stem cell transplantation
  • TREATMENT INCLUSION
  • Any patient regardless of sex or age with CD19+ B-ALL undergoing allogeneic HSCT (Group A) OR any patient regardless of sex or age with CD19+ B-CLL or NHL undergoing allogeneic HSCT (Group B)
  • Residual disease at the time of transplant (bulky or minimal) or post transplant relapse as evidenced by polymerase chain reaction (PCR) positivity, specific cytogenetic abnormalities, an abnormal population on flow cytometry or increased blasts on bone marrow biopsy or in the peripheral blood; minimal residual disease (MRD) will be defined as detection in blood or marrow of any of the following: * Any leukemia specific marker (such as t(9:22) or t(4:11)) documented in the patient’s leukemia cells pre transplant on a post transplant evaluation * An immune globulin rearrangement known to be a disease marker for this patient post transplant * A leukemia specific phenotype post transplant at a level of ≥ 0.01% * Mixed donor chimerism (any level)
  • Life expectancy ≥ 6 weeks
  • Karnofsky/Lansky score ≥ 50%
  • Bilirubin ≤ 2 times the upper limit of normal
  • Aspartate aminotransferase (AST) ≤ 3 times the upper limit of normal
  • Estimated glomerular filtration rate (GFR) > 50 mL/min
  • Hemoglobin (Hgb) > 8.0 (can be transfused)
  • Pulse oximetry of > 90% on room air
  • Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded; the male partner should use a condom
  • Available allogeneic activated peripheral blood T cell products with ≥ 15% expression of CD19.CAR-CD28zeta determined by flow cytometry (cell dose is based on total cell numbers and not individual anti-leukemic cell numbers)
  • No other investigational antitumor therapy for one month prior to entry in this study
  • Patients or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects; patients or their guardians will be given a copy of the consent form

Exclusion Criteria

  • TREATMENT EXCLUSION
  • Severe intercurrent infection
  • Evidence of graft versus host disease (GVHD) > grade II
  • Pregnant or lactating
  • History of hypersensitivity reactions to murine protein-containing products
  • Currently taking corticosteroids (> 0.5 mg/kg/day prednisone or equivalent) for therapy of GVHD

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
Contact: Carlos Almeida Ramos
Phone: 832-824-4817
Center for Cell and Gene Therapy
Status: ACTIVE
Contact: Carlos Almeida Ramos
Phone: 832-824-4817
Texas Children's Hospital
Status: ACTIVE
Contact: Carlos Almeida Ramos
Phone: 832-824-4817

PRIMARY OBJECTIVES:

I. To evaluate the safety and persistence of escalating doses of CD19CAR-CD28zeta-4-1BB-expressing Allogeneic T Lymphocytes (allogeneic- CD3/CD28 activated peripheral blood T lymphocytes [ATL]) genetically modified to express artificial T-cell receptors (CAR) targeting the CD19 molecule (CD19.CAR), given for prophylaxis, persistence or relapse of high risk B-cell malignancies post hematopoietic stem cell transplant (HSCT). Cells will be infused in a lymphodepleted environment.

SECONDARY OBJECTIVES:

I. To evaluate the effects of gene modified ATL on measurable disease.

II. To evaluate the impact of the gene modified ATL on virus-specific T-lymphocyte immune reconstitution.

III. To evaluate the impact of the gene modified ATL on normal CD19+ B-cell immune reconstitution post-hematopoietic stem cell transplant (HSCT).

OUTLINE: This is a dose-escalation study.

Participants receive CD19.CAR T cells intravenously (IV) over 10 minutes during day 0. Participants experiencing benefit after 6 weeks may receive up to 5 additional doses of CD19.CAR T cells at least 4-6 apart.

After completion of study treatment, participants are followed up 3, 6, 9, and 12 months, every 6 months for 4 years, and then annually for up to 15 years.

Trial Phase Phase I

Trial Type Treatment

Lead Organization
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center

Principal Investigator
Carlos Almeida Ramos

  • Primary ID CARPASCIO
  • Secondary IDs NCI-2018-00704, H-33133
  • Clinicaltrials.gov ID NCT02050347