CD19 Chimeric Antigen Receptor (CAR) T Cells for Adults With Recurrent or Refractory B Cell Malignancies

STATUS

Recruiting
End date

Dec 31, 2034
participants needed

24
sponsor

Loyola University

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Updated on 19 February 2024

See if I qualify

cancer

rheumatoid arthritis

lupus

blood transfusion

platelet count

heart disease

measurable disease

gilbert's syndrome

anticoagulation therapy

cyclophosphamide

ejection fraction

immunosuppression

immunosuppressive agents

lymphoid leukemia

fludarabine

graft versus host disease

lymphoma

filgrastim

flow cytometry

systemic therapy

autoimmune disease

systemic disease

leukemia

unstable angina

angina pectoris

b-cell lymphoma

leukapheresis

immunodeficiency

hepatitis b

bone marrow procedure

recurrent disease

alt/ast

apheresis

b-cell acute lymphoblastic leukemia

adult acute lymphocytic leukemia

hepatitis c

absolute lymphocyte count

primary immunodeficiency

immediate hypersensitivity reaction

acute lymphoblastic leukemia

b-cell lymphoma refractory

cns disorder

b-cell adult acute lymphoblastic leukemia

primary immune deficiency disorder

b-cell lymphoma recurrent

Summary

In this protocol, the investigators hypothesize that modifying the process of producing CAR+ T-cells can help to improve responses and reduce toxicities. Building on previous in vitro studies that have shown successful production of CAR+ T-cells using a new production approach, the investigators are now studying the ability to produce these CAR+ T-cells and determine how well they work in the clinical setting.

Description

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day and the cells will be transduced with an in house designed CAR retroviral vector. Participants will receive daily intravenous (IV) infusion of lymphodepleting regimen of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. Participants will receive the CAR transduced T cells IV infusion in the BMT Inpatient Unit and remain admitted for close monitoring for at least the first 7 days following the cell infusion (D0 to Day +7), possibly longer if any side effects are encountered. The CAR transduced T cells will be escalated from 1 x 106 transduced T cells/kg ( 20%) to 2 x 106 transduced T cells/kg ( 20%) in a Phase I design, based on toxicity. Once discharged from the inpatient unit, for the next 7 days (Day +8 to Day +14) the patients will be evaluated in the High Dose Unit (labs and physical exam) to screen for toxicities.

Details

Condition	B-Cell Acute Lymphoblastic Leukemia, Adult, B-cell Lymphoma Refractory, B-cell Lymphoma Recurrent
Age	18-100 years
Treatment	Cyclophosphamide, Fludarabine, CD19-CD34 CAR transduced T cells
Clinical Study Identifier	NCT04214886
Sponsor	Loyola University
Last Modified on	19 February 2024

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Eligibility		Yes	No	Not Sure
Inclusion Criteria
	Participants must be greater than or equal to 18 years of age
	Participants must have Eastern cooperative oncology group (ECOG) performance status of 0 or 1, or Karnofsky greater than or equal to 80%
	Participants must have been diagnosed with histologically confirmed aggressive B cell NHL that is refractory / recurrent
	Participants must have been diagnosed with histologically confirmed B-ALL that is refractory / recurrent
	Adequate performance status; adequate organ and marrow function as defined by (supportive care is allowed per institutional standards, i.e. filgrastim, transfusion)
	ANC 750/uL
	Platelet count 50,000/uL
	Absolute lymphocyte count 150/uL
	Adequate renal, hepatic, pulmonary and cardiac function defined as
	SaO2 92% on room air
	Creatinine 2 mg/dL or Creatinine Clearance 60 mL/min (as estimated by Cockcroft Gault)
	Total bilirubin 1.5 mg/dL (except in subjects with Gilbert's disease) (Elevations related to leukemia or lymphoma involvement of the liver will not disqualify a subject)
	Serum ALT/AST 3x ULN or 5X if there is hepatic involvement due to malignancy
	Cardiac ejection fraction (LVEF) 45%)
	Subjects with ALL or B-NHL with CNS1, or CNS1a, 2b, 2c are eligible only in the absence of neurologic symptoms suggestive of CNS disease involvement such as cranial nerve palsy
	If patients previously had CNS disease and are disease free after treatment with no clinical concerns for recurrent disease they are eligible for enrollment
	Subjects with history of allogeneic SCT must be at least 100 days from SCT, have no evidence of Graft versus Host Disease (GvHD), and no longer taking immunosuppressive agents for at least 30 days prior to enrollment. However, patients with grade 1 skin GVHD or low grade cGHVD <3 who are not requiring systemic therapy are eligible
	Females of child bearing potential and males of child fathering potential must be willing to practice birth control during and for 4 months post therapy
	Females of child bearing potential must have negative pregnancy test
	Must meet wash out period since prior therapies
	At least 2 weeks or 5 half-lives, whichever is shorter, must have elapsed since any prior systemic therapy at the time the subject is planned for leukapheresis, except for systemic inhibitory/stimulatory immune checkpoint therapy, which requires 5 half-lives
	Must have recovered from acute side effects from prior therapy to meet eligibility
	If had prior CAR therapy, 30 days must have elapsed prior to apheresis; may not have evidence of persistence of CAR T cells in blood samples (circulating levels of genetically modified cells of 5% by flow cytometry)
	No active HIV or active HBV/HCV infection. Patients with history of HBV or HCV who are PCR negative after appropriate therapy are eligible. Patients may not have any other uncontrolled, symptomatic, intercurrent illness
	No history of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study
	No active CNS disorder, or history of MI, cardiac angioplasty or stenting, unstable angina or other clinically significant cardiac disease with 12 months of enrollment, or have cardiac atrial or ventricular lymphoma involvement
	Not receiving anticoagulation therapy
	Not have primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
Exclusion Criteria
	Participants must not have an active bacterial, viral, fungal or other infection
	Participants must not have a history of HIV or current hepatitis B or hepatitis C virus
	Participants must not have a history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, or other clinically significant cardiac disease within 12 months of enrollment, or have cardiac atrial or cardiac ventricular lymphoma involvement
	No history of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study
	No active CNS disorder, or history of MI, cardiac angioplasty or stenting, unstable angina or other clinically significant cardiac disease with 12 months of enrollment, or have cardiac atrial or ventricular lymphoma involvement
	Not receiving anticoagulation therapy
	Not have primary immunodeficiency or history of autoimmune disease (e.g. Crohns, rheumatoid arthritis, systemic lupus) resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 2 years
	History of malignancy other than non-melanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, and breast) unless disease free for at least 1 year. Patients who are on adjuvant therapy with no evidence of active disease are deemed eligible for the trial

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anticoagulation therapy

cyclophosphamide

ejection fraction

immunosuppression

immunosuppressive agents

lymphoid leukemia

fludarabine

graft versus host disease

bone marrow procedure

recurrent disease

alt/ast

apheresis

b-cell acute lymphoblastic leukemia

adult acute lymphocytic leukemia

hepatitis c

absolute lymphocyte count

primary immunodeficiency

immediate hypersensitivity reaction

acute lymphoblastic leukemia

b-cell lymphoma refractory

cns disorder

b-cell adult acute lymphoblastic leukemia

primary immune deficiency disorder

b-cell lymphoma recurrent

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Study Definition

Wikipedia

CD19 Chimeric Antigen Receptor (CAR) T Cells for Adults With Recurrent or Refractory B Cell Malignancies