CD5.CAR/28 T Cells, Cyclophosphamide, and Fludarabine in Treating Participants with Recurrent T-Cell Malignancies Expressing the CD5 Antigen
This phase I trial studies the side effects and best dose of autologous (derived from cells collected from the patient) or allogeneic (derived from previous stem cell transplantation donors cells) 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 GROUP A: Suitable for allogeneic HSCT with confirmation of an identified eligible allogeneic (allo)-HSCT donor by a Foundation for the Accreditation of Cellular Therapy (FACT) accredited transplant center GROUP B: Relapsed post-allogeneic HSCT with previous HSCT donor from whom allogeneic MAGENTA CAR T cells can be manufactured 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: Age ≤ 75 years old. The first six (6) patients treated on the study should be adults (≥ 18 years [yrs] of age)
- INCLUSION - PROCUREMENT: Hemoglobin (Hgb) > 7.0 (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 GROUP A: Suitable for allogeneic hematopoietic stem cell transplant (HSCT) with confirmation of an identified eligible allo-HSCT donor by FACT accredited institution GROUP B: Relapsed post-allogeneic HSCT with previous HSCT donor from whom allogeneic MAGENTA CAR T cells can be manufactured AND * 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: Age ≤ 75 years old. NOTE: The first six (6) patients treated on the study should be adults (≥ 18 yrs of age)
- 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: ≥ 60 days post-allogeneic HSCT at time of treatment
- 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: 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
- EXCLUSION - TREATMENT: Clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, Adv, BK-virus, or HHV-6
- EXCLUSION - TREATMENT: Evidence of acute GVHD > Grade II or active chronic GVHD > mild global severity score
- EXCLUSION - TREATMENT: Currently taking corticosteroids for therapy of GVHD at a dose of > 0.5mg/kg prednisone equivalent
- EXCLUSION - TREATMENT: Patients who have received Immunosuppressive Treatment (IST) for GVHD within 28 days of infusion
- EXCLUSION - TREATMENT: Patients who have received donor lymphocyte infusion (DLI) within 28 days of infusion
- EXCLUSION - TREATMENT: Any of the following cardiac criteria: atrial fibrillation/flutter; myocardial infarction within the last 12 months; prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF =< 30% or LVEF =< 50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA III or IV (Confirmation of absence of these conditions within 12 months of treatment)
- 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
Additional locations may be listed on ClinicalTrials.gov for NCT03081910.
Locations matching your search criteria
United States
Texas
Houston
PRIMARY OBJECTIVES:
I. To evaluate the safety of escalating doses of autologous (group A) or allogeneic hematopoietic stem cell transplant (HSCT) donor-derived (group B) peripheral blood 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 evaluate whether elimination of T cell leukemia or lymphoma by CD5 CAR T cells will allow patients previously ineligible for HSCT due to residual disease to proceed to curative allogeneic HSCT.
II. To evaluate whether elimination of T cell leukemia or lymphoma by CD5 CAR T cells will allow patients who have relapsed post-allogeneic HSCT to proceed to subsequent allogeneic HSCT.
III. To evaluate whether elimination of T cell leukemia or lymphoma by CD5 CAR T cells will allow patients who have relapsed post-allogeneic HSCT to proceed to subsequent allogeneic HSCT.
OUTLINE: This is a dose escalation study of autologous CD5-specific CAR-28 zeta CAR T-cells and allogeneic CD5-specific CAR-28 zeta CAR T-cells. Patients who have not previously received HSCT are assigned to group A, patients who have relapsed after HSCT are assigned to group B.
GROUP A: Participants receive cyclophosphamide intravenously (IV) over 1 hour daily and fludarabine IV over 30 minutes daily for 3 days, finishing at least 24 hours before receiving autologous CD5-specific CAR-28 zeta CAR T-cells IV over 1-10 minutes on day 0. Patients undergo echocardiography during screening, undergo blood sample collection throughout the study and may undergo positron emission tomography (PET) scan, computed tomography (CT) scan, magnetic resonance imaging (MRI) and/or nuclear imaging throughout the study.
GROUP B: Participants receive cyclophosphamide IV over 1 hour daily and fludarabine IV over 30 minutes daily for 3 days, finishing at least 24 hours before receiving allogeneic CD5-specific CAR-28 zeta CAR T-cells IV over 1-10 minutes on day 0. Patients undergo echocardiography during screening, undergo blood sample collection throughout the study and may undergo PET scan, CT scan, MRI and/or nuclear imaging throughout the study.
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 PhasePhase I
Trial Typetreatment
Lead OrganizationBaylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Principal InvestigatorRayne Helen Rouce
- Primary IDMAGENTA
- Secondary IDsNCI-2018-00726, H-40466
- ClinicalTrials.gov IDNCT03081910