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CD5.CAR / 28 T Cells, Cyclophosphamide, and Fludarabine in Treating Participants with Recurrent T-Cell Malignancies Expressing the CD5 Antigen

Trial Status: Active

This phase I trial studies the side effects and best dose of autologous CD5-specific CAR-28 zeta CAR T-cells (CD5.CAR / 28 T cells) when given together with cyclophosphamide and fludarabine in treating participants with T-cell cancers expressing the CD5 antigen that that has come back. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. The antibody used in this study is called anti-CD5, which sticks to T-cell leukemia or lymphoma cells because of a substance on the outside of these cells called CD5. The T cells will also contain a substance called CD28 which may help stimulate the T cells and may make them last longer. Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving CD5.CAR / 28 T cells with cyclophosphamide and fludarabine may work better in treating participants with T-cell malignancies expressing the CD5 antigen.

Inclusion Criteria

  • INCLUSION - PROCUREMENT: Referred patients will initially be consented for procurement of blood for generation of the transduced ATL; eligibility criteria at this stage include: * Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including angioimmunoblastic T-cell lymphoma [AITL], enteropathy-associated T-cell lymphoma [EATL], monomorphic epitheliotropic intestinal T-cell lymphoma [MEITL], peripheral T-cell lymphoma [PTCL] not otherwise specified [NOS], anaplastic large cell lymphoma [ALCL] adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, extranodal natural killer [NK]/T cell lymphoma, mycosis fungoides/ Sezary syndrome stage IIb or higher) AND * suitable for allogeneic hematopoietic stem cell transplant (HSCT) ** with confirmation of an identified eligible allogeneic (allo)-HSCT donor by a Foundation for the Accreditation of Cellular Therapy (FACT) accredited transplant center AND ** with confirmation that the center plans to proceed with transplant if CD5.CAR treatment induces a complete remission * For T-NHL subjects, eligibility will be confined to disease stages where allogeneic HSCT is indicated
  • INCLUSION - PROCUREMENT: CD5-positive tumor (result can be pending at this time); > 50% CD5 + blasts by flow cytometry or immunohistochemistry (tissue) assessed by a Clinical Laboratory Improvement Amendments (CLIA) certified flow cytometry/pathology laboratory
  • INCLUSION - PROCUREMENT: The first six (6) patients treated on the study should be adults (≥ 18 years [yrs] of age); six adolescents (age 12-18) should be treated before children (≥ 3 yrs of age) are eligible
  • INCLUSION - PROCUREMENT: Hemoglobin (Hgb) > 8.0 (can be transfused)
  • INCLUSION - PROCUREMENT: Life expectancy greater than 12 weeks
  • INCLUSION - PROCUREMENT: If pheresis required to collect blood: * Creatinine <1.5 × upper limit normal
  • INCLUSION - PROCUREMENT: If pheresis required to collect blood: * Aspartate aminotransferase (AST) < 1.5 × upper limit normal
  • INCLUSION - PROCUREMENT: If pheresis required to collect blood * Prothrombin time (PT) and activated partial thromboplastin time (APTT) <1.5 × upper limit normal
  • INCLUSION - PROCUREMENT: Informed consent explained to, understood by and signed by patient/guardian; patient/guardian given copy of informed consent
  • INCLUSION - TREATMENT: Diagnosis of recurrent T-cell acute lymphoblastic leukemia (T-ALL), T-cell acute lymphoblastic lymphoma (T-LLy), or T-non-Hodgkin lymphoma (T-NHL, including angioimmunoblastic T-cell lymphoma [AITL], enteropathy-associated T-cell lymphoma [EATL], monomorphic epitheliotropic intestinal T-cell lymphoma [MEITL], peripheral T-cell lymphoma [PTCL] NOS, anaplastic large cell lymphoma [ALCL], adult T-cell leukemia/lymphoma, T cell prolymphocytic leukemia with symptomatic disease, extranodal NK/T cell lymphoma, mycosis fungoides/ Sezary syndrome stage IIB or higher) AND * suitable for allogeneic hematopoietic stem cell transplant (HSCT) ** with confirmation of an identified eligible allo-HSCT donor by a FACT accredited transplant center AND ** with confirmation that the center plans to proceed with transplant if CD5.CAR treatment induces a complete remission * For T-NHL subjects, eligibility will be confined to disease stages where allogeneic HSCT is indicated
  • INCLUSION - TREATMENT: CD5-positive tumor (> 50%) CD5+ blasts by flow cytometry or immunohistochemistry (tissue) assessed in a CLIA certified flow cytometry/pathology laboratory
  • INCLUSION - TREATMENT: The first six (6) patients treated on the study should be adults (≥ 18 yrs of age); six adolescents (age 12-18) should be treated before children (≥ 3 yrs of age) are eligible
  • INCLUSION - TREATMENT: Bilirubin less than 3 times the upper limit of normal
  • INCLUSION - TREATMENT: AST less than 5 times the upper limit of normal
  • INCLUSION - TREATMENT: Estimated glomerular filtration rate (GFR) > 60 mL/min
  • INCLUSION - TREATMENT: Pulse oximetry of > 90% on room air
  • INCLUSION - TREATMENT: Karnofsky or Lansky score of > 60%
  • INCLUSION - TREATMENT: Recovered from acute toxic effects of prior chemotherapy at least one week before entering this study
  • INCLUSION - TREATMENT: Available autologous activated peripheral blood T cell products with ≥ 20% expression of CD5.CAR.28 zeta and < 0.5% gene-modified malignant T blasts by flow cytometry
  • INCLUSION - TREATMENT: Life expectancy of greater than 12 weeks
  • INCLUSION - TREATMENT: 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
  • INCLUSION - TREATMENT: Informed consent explained to, understood by, and signed by patient/guardian; patient/guardian given copy of informed consent

Exclusion Criteria

  • EXCLUSION - PROCUREMENT: Active infection requiring antibiotics
  • EXCLUSION - PROCUREMENT: Active infection with human immunodeficiency virus (HIV) or human T-lymphotropic virus (HTLV)
  • EXCLUSION - PROCUREMENT: Clinically significant viral infection or uncontrolled viral reactivation of Epstein Barr virus (EBV), cytomegalovirus (CMV), adenovirus (Adv), BK-virus, or human herpesvirus 6 (HHV-6)
  • EXCLUSION - PROCUREMENT: Cardiac criteria: prolonged QT syndrome; atrial fibrillation/flutter; myocardial infarction within the last 12 months; cardiac echocardiography with left ventricular systolic function (LVSF) ≤ 30% or left ventricular ejection fraction (LVEF) ≤ 50%; cardiac dysfunction New York Heart Association (NYHA) III or IV; cardiac echocardiography with clinically significant pericardial effusion
  • EXCLUSION - PROCUREMENT: History of other cancer (except non-melanoma skin cancer or in situ breast cancer or cervix cancer) unless the tumor was successfully treated with curative intent at least 2 years before trial entry
  • EXCLUSION - TREATMENT: Currently receiving any investigational agents or having received any tumor vaccines within the previous 6 weeks
  • EXCLUSION - TREATMENT: History of hypersensitivity reactions to murine protein-containing products
  • EXCLUSION - TREATMENT: Pregnant or lactating
  • EXCLUSION - TREATMENT: Tumor in a location where enlargement could cause airway obstruction
  • EXCLUSION - TREATMENT: Active infection with HIV or HTLV
  • EXCLUSION - TREATMENT: Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6
  • EXCLUSION - TREATMENT: Cardiac criteria: prolonged QT syndrome; atrial fibrillation/flutter; myocardial infarction within the last 12 months; cardiac echocardiography with LVSF ≤ 30% or LVEF ≤ 50%; cardiac dysfunction NYHA III or IV; cardiac echocardiography with clinically significant pericardial effusion
  • EXCLUSION - TREATMENT: Central nervous system (CNS) abnormalities: presence of CNS-3 disease defined as detectable cerebrospinal blast cells in a sample of cerebrospinal fluid (CSF) with ≥ 5 white blood cells (WBCs) per mm^3; history or presence of any CNS disorder such as a seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

Texas

Houston
Baylor College of Medicine / Dan L Duncan Comprehensive Cancer Center
Status: ACTIVE
Contact: Rayne Helen Rouce
Phone: 832-824-4716
Center for Cell and Gene Therapy
Status: ACTIVE
Contact: Rayne Helen Rouce
Phone: 832-824-4716
Texas Children's Hospital
Status: ACTIVE
Contact: Rayne Helen Rouce
Phone: 832-824-4716

PRIMARY OBJECTIVES:

I. To evaluate the safety of escalating doses of autologous peripheral blood T lymphocytes (activated T lymphocytes [ATLs]) genetically modified to express chimeric antigen receptors (CAR) targeting the CD5 molecule (CD5.CAR) in combination with lymphodepletion in patients with relapsed/refractory T-cell malignancies.

SECONDARY OBJECTIVES:

I. To measure the anti-tumor effects of CD5.CAR-ATLs in patients with T-cell leukemia or lymphoma.

EXPLORATORY OBJECTIVES:

I. To measure the survival and function of CD5.CAR-ATLs in vivo.

II. To evaluate whether elimination of T cell leukemia or lymphoma by CD5 CAR T cells will allow patients previously ineligible for hematopoietic stem cell transplant (HSCT) due to residual disease to proceed to curative allogeneic HSCT.

OUTLINE: This is a dose escalation study of autologous CD5-specific CAR-28 zeta CAR T-cells.

Participants receive cyclophosphamide infusion over 1 hour daily and fludarabine infusion over 30 minutes daily for 3 days, finishing at least 24 hours before receiving autologous CD5-specific CAR-28 zeta CAR T-cells intravenously (IV) over 1-10 minutes on day 0.

After completion of study treatment, participants are followed up at weeks 1, 2, 3, 4, 6, and 8, and months 3, 6, 9, and 12. Then, they are followed up every 6 months for 4 years and then yearly for 10 more years.

Trial Phase Phase I

Trial Type Treatment

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

Principal Investigator
Rayne Helen Rouce

  • Primary ID MAGENTA
  • Secondary IDs NCI-2018-00726
  • Clinicaltrials.gov ID NCT03081910