Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03434769
Recruitment Status : Recruiting
First Posted : February 15, 2018
Last Update Posted : September 26, 2018
Sponsor:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center

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.

Condition or disease Intervention/treatment Phase
Non-Hodgkin Lymphoma Drug: Cyclophosphamide Drug: Fludarabine Biological: CAR-T Cells Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 18 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Clinical Trial of AntiCD19 Chimeric Antigen Receptor T Cells for Treatment of Relapsed or Refractory Non Hodgkin Lymphoma
Actual Study Start Date : May 2, 2018
Estimated Primary Completion Date : April 2021
Estimated Study Completion Date : July 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arm Intervention/treatment
Experimental: 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
Drug: Cyclophosphamide
Cyclophosphamide 60mg/Kg on day -6

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

Biological: CAR-T Cells
Chimeric antigen receptor T cells on day 0




Primary Outcome Measures :
  1. Number of patients with Lymphoma response [ Time Frame: Up to 12 months after getting CAR-T infusion ]
    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).


Secondary Outcome Measures :
  1. Duration of response [ Time Frame: Up to 12 months after getting CAR-T infusion ]
    This is measured, only in responders, from the documented beginning of response (CR or PR) to the time of relapse.

  2. Disease-free survival [ Time Frame: Up to 12 months after getting CAR-T infusion ]
    Survival is defined as the date of study entry to the date of death. Disease-free survival is measured from the time of occurrence of disease-free state to disease recurrence or death from lymphoma or acute toxicity of treatment.

  3. Disease-specific survival [ Time Frame: Up to 12 months after getting CAR-T infusion ]
    To minimize the risk of bias, the event should be recorded as death from lymphoma, or from toxicity from the drug. Death from unknown causes should be attributed to the drug.

  4. Progression-free survival [ Time Frame: Up to 12 months after getting CAR-T infusion ]
    Progression-free Survival (PFS) is defined as the time from entry onto study until lymphoma progression or death from any cause.

  5. Time to progression [ Time Frame: Up to 12 months after getting CAR-T infusion ]
    Time to progression (TTP) is defined as the time from study entry until lymphoma progression or death due to lymphoma.

  6. Time to treatment failure [ Time Frame: Up to 12 months after getting CAR-T infusion ]
    Time to treatment failure (event-free survival) is measured from the time from study entry to any treatment failure including discontinuation of treatment for any reason



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03434769


Contacts
Layout table for location contacts
Contact: Paolo F Caimi, MD 800-241-6422 paolo.caimi@uhhospitals.org

Locations
Layout table for location information
United States, Ohio
University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106-5065
Contact: Paolo F. Caimi, MD    800-241-6422    paolo.caimi@case.edu   
Principal Investigator: Paolo F. Caimi, MD         
Sponsors and Collaborators
Case Comprehensive Cancer Center
Investigators
Layout table for investigator information
Principal Investigator: Paolo F Caimi, MD University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center

Layout table for additonal information
Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT03434769     History of Changes
Other Study ID Numbers: CASE2417
First Posted: February 15, 2018    Key Record Dates
Last Update Posted: September 26, 2018
Last Verified: September 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Case Comprehensive Cancer Center:
Cyclophosphamide
Fludarabine
Chimeric antigen receptor T cells

Additional relevant MeSH terms:
Layout table for MeSH terms
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents