AntiCD19 Chimeric Antigen Receptor T Cells for Relapsed or Refractory Non Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT03434769|
Recruitment Status : Active, not recruiting
First Posted : February 15, 2018
Last Update Posted : January 25, 2023
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|Condition or disease||Intervention/treatment||Phase|
|Non-Hodgkin Lymphoma||Drug: Cyclophosphamide Drug: Fludarabine Biological: CAR-T Cells||Phase 1|
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
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||31 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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 :||July 9, 2018|
|Estimated Primary Completion Date :||April 1, 2023|
|Estimated Study Completion Date :||July 1, 2023|
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
Cyclophosphamide 60mg/Kg on day -6
Fludarabine 25mg/m^2 IV on days -5 to -3
Other Name: Fludara
Biological: 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)
- 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).
- 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.
- 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.
- 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.
- 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.
- 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.
- 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
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|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
- 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.
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
|United States, Missouri|
|Washington University School of Medicine|
|Saint Louis, Missouri, United States, 63110|
|United States, Ohio|
|University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center|
|Cleveland, Ohio, United States, 44106|
|Principal Investigator:||Benjamin Tomlinson, MD||University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center|
|Responsible Party:||Benjamin Tomlinson, Principal Investigator, Case Comprehensive Cancer Center|
|Other Study ID Numbers:||
|First Posted:||February 15, 2018 Key Record Dates|
|Last Update Posted:||January 25, 2023|
|Last Verified:||January 2023|
|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|
Chimeric antigen receptor T cells
Neoplasms by Histologic Type
Immune System Diseases
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Molecular Mechanisms of Pharmacological Action