AntiCD19 Chimeric Antigen Receptor T Cells for Relapsed or Refractory Non Hodgkin Lymphoma

NCT ID: NCT03434769

Last Updated: 2025-01-06

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 31 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-09
• Study Completion Date: 2036-02-29

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.

Conditions

Non-Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells

Lymphodepletive regimen, consisting of Cyclophosphamide 60mg/kg IV on day -6 and Fludarabine 25mg/m2 IV on days -5 to -3. Followed by infusion of Chimeric antigen receptor T-cells (CAR-T) on day 0

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide 60mg/Kg on day -6

Fludarabine

Intervention Type: DRUG

Fludarabine 25mg/m\^2 IV on days -5 to -3

CAR-T Cells

Intervention Type: BIOLOGICAL

Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0

Level -1 (1 x 105 cells/kg)

Level 1 [Starting dose] (5 x 105 cells/kg)

Level 2 (1 x 106 cells/kg)

Level 3 (2 x 106 cells/kg)

Interventions

Cyclophosphamide

Cyclophosphamide 60mg/Kg on day -6

Intervention Type: DRUG

Fludarabine

Fludarabine 25mg/m\^2 IV on days -5 to -3

Intervention Type: DRUG

CAR-T Cells

Chimeric antigen receptor T cells to be implemented in a "3 + 3" design on day 0

Level -1 (1 x 105 cells/kg)

Level 1 [Starting dose] (5 x 105 cells/kg)

Level 2 (1 x 106 cells/kg)

Level 3 (2 x 106 cells/kg)

Intervention Type: BIOLOGICAL

Other Intervention Names

Cytoxan; Endoxan; Neosar; Procytox; Revimmune; Cycloblastin; Fludara

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Benjamin Tomlinson

OTHER

Sponsor Role: lead

Responsible Party

Benjamin Tomlinson

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Benjamin Tomlinson, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Locations

Washington University School of Medicine

St Louis, Missouri, United States

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, United States

Countries

United States

References

Ghobadi A, Caimi PF, Reese JS, Goparaju K, di Trani M, Ritchey J, Jackson Z, Tomlinson B, Schiavone JM, Kleinsorge-Block S, Zamborsky K, Eissenberg L, Schneider D, Boughan KM, Zabor EC, Metheny L, Gallogly M, Kruger W, Kadan M, Worden A S A, Sharma A, Cooper BW, Otegbeye F, Sekaly RP, Wald DN, Carlo-Stella C, DiPersio J, Orentas R, Dropulic B, de Lima M. Treatment of non-Hodgkin lymphoma with point-of-care manufactured CAR T cells: a dual institution, phase 1 trial. EClinicalMedicine. 2025 Mar 4;81:103138. doi: 10.1016/j.eclinm.2025.103138. eCollection 2025 Mar.

Reference Type: DERIVED

PMID: 40115173 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34893603 (View on PubMed)

Other Identifiers

CASE2417

Identifier Type: -

Identifier Source: org_study_id