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

NCT03434769 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: CASE2417
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

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.

Conditions

Non-Hodgkin Lymphoma

Keywords

Cyclophosphamide; Fludarabine; Chimeric antigen receptor T cells

Outcome Measures

Primary Outcomes (1)

• Number of patients with Lymphoma response

  The 2014 Lugano Response for Malignant Lymphoma will be used the following categories of response: : Complete Response (CR), Partial Response (PR), Stable Disease (SD), Relapse and Progression (PD).

  Up to 12 months after getting CAR-T infusion

Secondary Outcomes (6)

• Duration of response

  Up to 12 months after getting CAR-T infusion

• Disease-free survival

  Up to 12 months after getting CAR-T infusion

• Disease-specific survival

  Up to 12 months after getting CAR-T infusion

• Progression-free survival

  Up to 12 months after getting CAR-T infusion

• Time to progression

  Up to 12 months after getting CAR-T infusion

Study Arms (1)

Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells

EXPERIMENTAL

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

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: CAR-T Cells

Interventions

Cyclophosphamide DRUG

Cyclophosphamide 60mg/Kg on day -6

Also known as: Cytoxan, Endoxan, Neosar, Procytox, Revimmune, Cycloblastin

Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells

Fludarabine DRUG

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

Also known as: Fludara

Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells

CAR-T Cells 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)

Cyclophosphamide + Fludarabine + Infusion of CAR-T Cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Benjamin Tomlinson: lead

Study Sites (2)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Related Publications (2)

• 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.

  PMID: 40115173 DERIVED

• 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.

  PMID: 34893603 DERIVED

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate; Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Benjamin Tomlinson, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 9, 2018
• First Posted: February 15, 2018
• Study Start: July 9, 2018
• Primary Completion: March 1, 2023
• Study Completion (Estimated): February 1, 2036
• Last Updated: February 27, 2026

Record last verified: 2026-02

Locations

US (2)