Clinical trial NCT03434769: AntiCD19 Chimeric Antigen Receptor T Cells for Relapsed or Refractory Non Hodgkin Lymphoma
Official title: Phase I Clinical Trial of AntiCD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non Hodgkin Lymphoma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Non-Hodgkin Lymphoma
Keywords: Cyclophosphamide
Fludarabine
Chimeric antigen receptor T cells
Lead sponsor: Case Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2018-02-15
Enrollment: 31
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine if it is possible to treat your cancer with a new type of T cell-based immunotherapy (therapy that uses your immune system to treat the cancer). T cells are a type of white blood cell that helps the body fight infections. This treatment uses T cells already present within your body that have been modified outside of the body and returned to target your cancer. This type of treatment is sometimes referred to as adoptive cell transfer (ACT). In this study the specific type of cells that will be used is called chimeric antigen receptor T cells (CAR T cells). Another purpose of this study is to learn about the side effects and toxicities related to this treatment.

Detailed description: Primary Objective: To determine the safety of the treatment of relapsed or refractory B cell lymphomas with chimeric antigen receptor T cells targeting cluster of differentiation antigen 19 (CD19) and to find the recommended phase II dose for this cellular therapy

Secondary Objectives

* To describe the safety profile of the infusion of CAR-T cells targeting CD19.
* To describe the toxicities related to infusion of CAR-T cells targeting CD19.
* To describe the overall response rate and complete response rate of relapsed B cell malignancies treated with CAR-T cells targeting CD19.

Eligibility criteria: Inclusion Criteria:

* Subjects must have relapsed or refractory non-Hodgkin lymphoma treated with at least two lines of therapy. Disease must have either progressed after the last regimen or presented failure to achieve partial or complete remission with the last regimen.
* The patient's lymphoma must be CD19 positive, either by immunohistochemistry or flow cytometry analysis on the last biopsy available.
* Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2
* Total bilirubin ≤ 1.5 times the institutional upper limit of normal
* Aspartate transaminase (AST or SGOT) ≤ 3 X institutional upper limit of normal
* Alanine transaminase (ALT or SGPT) ≤ 3 X institutional upper limit of normal
* Serum Creatinine ≤ 2 X the institutional upper limit of normal
* Subjects must have the following hematologic function parameters:

  * absolute neutrophil count (ANC)\>1,000/uL
  * Absolute Lymphocyte Count \>100/uL
  * Platelets \>50,000/uL
* Subjects must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* Autologous transplant within 6 weeks of planned CAR-T cell infusion
* History of allogeneic stem cell transplant.
* Recipient of CAR-T cell therapy outside of this protocol.
* Active central nervous system or meningeal involvement by lymphoma. Subjects with untreated brain metastases or central nervous system (CNS) disease will be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. Patients with a history of CNS or meningeal involvement must be in a documented remission by cerebrospinal fluid evaluation and contrast-enhanced MRI imaging for at least 90 days prior to registration.
* Active malignancy, other than non-melanoma skin cancer, carcinoma in situ (e.g. cervix, bladder, breast).
* HIV seropositivity
* Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, pulmonary abnormalities or psychiatric illness/social situations that would limit compliance with study requirements.
* Pregnant or breastfeeding women are excluded from this study because CAR-T cell therapy may be associated with the potential for teratogenic or abortifacient effects. Women of child bearing potential must have a negative serum pregnancy test. Because there is an unknown, but potential risk for adverse events in nursing infants secondary to treatment of the mother with CAR-T cells, breastfeeding should be discontinued. These potential risks may also apply to other agents used in this study.
* Evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia on any bone marrow biopsy prior to initiation of therapy
* Serologic status reflecting active hepatitis B or C infection. Patients that are positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) prior to enrollment. (PCR positive patients will be excluded.)
* Patients with history of clinically relevant CNS pathology such as epilepsy, seizure disorders, paresis, aphasia, uncontrolled cerebrovascular disease, severe brain injuries, dementia and Parkinson's disease.
* History of autoimmune disease (i.e. rheumatoid arthritis, systemic lupus erythematosus) with requirement of immunosuppressive medication within 6 months.

Primary outcomes:
measure: Number of patients with Lymphoma response
timeFrame: Up to 12 months after getting CAR-T infusion
Secondary outcomes:
measure: Duration of response
timeFrame: Up to 12 months after getting CAR-T infusion
measure: Disease-free survival
timeFrame: Up to 12 months after getting CAR-T infusion
measure: Disease-specific survival
timeFrame: Up to 12 months after getting CAR-T infusion
measure: Progression-free survival
timeFrame: Up to 12 months after getting CAR-T infusion
measure: Time to progression
timeFrame: Up to 12 months after getting CAR-T infusion
measure: Time to treatment failure
timeFrame: Up to 12 months after getting CAR-T infusion
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
state: Ohio
Study officials:
affiliation: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center
name: Benjamin Tomlinson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maschan M, Caimi PF, Reese-Koc J, Sanchez GP, Sharma AA, Molostova O, Shelikhova L, Pershin D, Stepanov A, Muzalevskii Y, Suzart VG, Otegbeye F, Wald D, Xiong Y, Wu D, Knight A, Oparaocha I, Ferencz B, Roy A, Worden A, Kruger W, Kadan M, Schneider D, Orentas R, Sekaly RP, de Lima M, Dropulic B. Multiple site place-of-care manufactured anti-CD19 CAR-T cells induce high remission rates in B-cell malignancy patients. Nat Commun. 2021 Dec 10;12(1):7200. doi: 10.1038/s41467-021-27312-6.