T Cells in Treating Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or B Cell Lymphomas
This phase I/IIa trial studies the side effects and best dose of T cells in treating patients with chronic lymphocytic leukemia or B cell lymphomasthat have come back after a period of improvement or do not respond to previous treatment. T cells modified in the laboratory may allow T cells to make a protein that helps to recognize and kill cancer cells.
Inclusion Criteria
- Patients must have the following CD19+ B cell leukemia or lymphoma either with relapsed or chemotherapy-refractory disease or with evidence of residual disease following therapy; in all cases, patient’s disease must be confirmed at Memorial Sloan-Kettering Cancer Center (MSKCC) * Chronic lymphocytic leukemia (CLL): Patients must have a diagnosis of CLL as evidenced by flow cytometry, bone marrow histology, and/or cytogenetics * Other low grade B-cell neoplasms are eligible for study, such as small lymphocytic lymphoma (SLL), follicular lymphoma, Waldenstrom’s macroglobulinemia, hairy cell leukemia, marginal zone lymphomas, and mantle cell lymphomas
- Creatinine =< 2.0 mg/100 ml
- Bilirubin =< 2.0 mg/100 ml
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3.0 x normal
- Prothrombin time (PT) and partial thromboplastin time (PTT) =< 2 x normal outside the setting of stable chronic anticoagulation therapy
- Adequate cardiac function (left ventricular ejection fraction [LVEF] >= 40%) as assessed by echocardiography (ECHO) or multigated acquisition (MUGA) scan performed within 1 month of treatment
- Adequate pulmonary function as assessed by >= 92% oxygen saturation on room air by pulse oximetry
- Life expectancy of > 3 months
Exclusion Criteria
- Karnofsky performance status < 70
- CLL patients with active transformed disease (Richter’s transformation) are ineligible for enrollment on this study
- Patients with following cardiac conditions will be excluded: * New York Heart Association (NYHA) stage III or IV congestive heart failure * Myocardial infarction =< 6 months prior to enrollment * History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration * History of severe non-ischemic cardiomyopathy with ejection fraction (EF) =< 20%
- Patients with human immunodeficiency virus (HIV), hepatitis B or hepatitis C infection are ineligible
- Patients with any concurrent active malignancies as defined by malignancies requiring any therapy other than expectant observation
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT00466531.
PRIMARY OBJECTIVES:
I. To assess the safety of autologous T cells genetically modified to express chimeric antigen receptor (CAR) targeting cluster of differentiation (CD)19 antigen (19-28z) with or without conditioning chemotherapy. (Phase I)
II. To compare the relative engraftment and persistence of the two CAR modified CD19-targeted T cells expressing different co-stimulatory signaling domain CD28 (19-28z) and 4-1BB (CART-19:CD3z-4-1BB) in the CAR construct. (Phase IIa)
SECONDARY OBJECTIVES:
I. To compare the in vivo survival of genetically modified 19-28z CAR+ T cells after T cell infusion alone or in combination with conditioning chemotherapy.
II. To compare the gene transfer/expression efficiency of the two viral vectors (retrovirus versus [vs.] lentivirus).
III. To assess the anti-leukemic activity of adoptively transferred CD19-targeted modified T cells linked to the CD28 (19-28z) and 4-1BB signaling domains (CART-19:CD3z-4-1BB).
OUTLINE: This is a phase I, dose-escalation study of anti-CD19-CAR retroviral vector-transduced autologous T cells followed by a phase IIa study.
PHASE I
Step 1: Patients receive anti-CD19-CAR retroviral vector-transduced autologous T cells intravenously (IV) over 15 minutes to 2 hours on day 0.
Step 2: Patients receive cyclophosphamide IV on day -2. Patients then receive anti-CD19-CAR retroviral vector-transduced autologous T cells IV over 15 minutes to 2 hours 2 days on days 0-1.
Step 3: Patients receive conditioning chemotherapy at the discretion of treating physician-2. Between 2-7 days following the completion of conditioning chemotherapy, patients receive anti-CD19-CAR retroviral vector-transduced autologous T cells IV over 15 minutes to 2 hours on days 0-1.
PHASE IIa: Patients receive conditioning chemotherapy at the discretion of investigator. Between 2-7 days following the completion of conditioning chemotherapy, patients receive anti-CD19-CAR retroviral vector-transduced autologous T cells IV over 15 minutes to 2 hours on days 0-1.
After completion of study treatment, patients are followed up weekly for 4 weeks, monthly for 6 months, and annually for up to 15 years.
Trial PhasePhase I/II
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorJae Park
- Primary ID06-138
- Secondary IDsNCI-2016-00935
- ClinicalTrials.gov IDNCT00466531