Development of CAR-T cells to treat malignant B neoplasms

Phase 1

• Conditions: ymphoma, Precursor B cell Lymphoblastic Leukemia, Precursor B cell Lymphoblastic Lymphoma, Adult T cell Leukemia and Lymphoma

• Registration Number: RBR-7cr9yvf
• Lead Sponsor: Hospital Israelita Albert Einstein

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-07-30
• Last Update Posted: 29 May 2023
• Study Completion: 2023-12-31

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: Not specified
• Target Recruitment: Not specified

Inclusion Criteria

Provision of the dated and signed free and informed consent form (IC); express willingness to comply with all study procedures and availability during the study; men or women; age 02 and 70 years; Good general health, proven by medical history; diagnosis of refractory or recurrent ALL or LLC and non-Hodgkin lymphoma; Ability to administer oral medications; for women with reproductive potential: use of highly effective contraceptive for at least 1 month before screening and agree to use a contraceptive method during participation in the study and for an additional 4 months after the completion of the administration of CAR T cells; for men with reproductive potential: use of condoms or other methods to ensure effective contraception with the partner; Agreement to adhere to Lifestyle Recommendations: Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, must use highly effective contraceptive methods at least 4 months after the infusion of CAR-T; Sexually active men must use a condom during sexual intercourse from the moment the project is signed for at least 4 months after the infusion of CAR-T. A condom is required for all sexually active male participants to prevent them from having a child and to prevent delivery of the study treatment via the seminal fluid to their partner. In addition, participants must not donate sperm. The subjects should attend the consultations, do the tests according to the protocol, use antibiotics and other medications as indicated. Individuals must have ALL, LLC or relapsed or refractory lymphoma treated with at least two lines of treatment. The disease must have progressed or show partial remission or the complete response must not have been achieved with the last regimen; individuals with Philadelphia Chromosome positive acute lymphoblastic leukemia (ALL + Ph) are eligible if they have progressed, have a stable or recurrent disease after two lines of treatment, including tyrosine kinase inhibitors (TKIs); Individuals with LNHDGCB (large B-cell non-Hodgkin's lymphoma) must have progressed, presented with stable disease or recurrence after initial treatment regimens that include an anthracycline and an anti-CD20 monoclonal antibody; Individuals with transformed LF (follicular lymphoma), LZM (mantle zone lymphoma) or LLC / ALL must have progressed, presented with stable disease or recurrence with transformed disease after initial treatment for LNHDCGB; Individuals who had a recurrence =12 months after treatment must have progressed after autologous transplantation or be ineligible for autologous transplantation; The patient's disease must be positive for CD19 by immunohistochemistry or flow cytometry analysis in the last available analysis; 2 to 70 years of age; General status: Adult individuals: ECOG less than or equal 2 for individuals over 16 years old; Lansky greater than or equal to 50% for individuals under 16 years old; Normal Functioning of Organs and Marrow (supportive treatment is allowed according to institutional rules, that is, filgrastim, transfusion): Total bilirubin = 2; AST (TGO) = 5 times the normal limit; ALT (TGP) = 5 times the normal limit; Serum Creatinine = 1.5; Pulse oximetry> 91% in room air; Absence of dyspnea or mild dyspnoea (= Grade 1); Forced expiratory volume in 1 s (FEV1) =50% or carbon monoxide diffusion test (DLCO) =50% of the predicted level; Left ventricular ejection fraction =45% confirmed by echocardiogram; individuals must hav

Exclusion Criteria

Autologous transplantation within 6 weeks of the planned infusion of CAR T cells; history of allogeneic stem cell transplantation of hematopoietic stem cells (HSCT) 4 months before the infusion; receiving treatment with CAR T cells outside this protocol; compromise of the active central or meningeal system by tumor. Individuals with untreated brain metastases / CNS disease will be excluded from this clinical study because of their unfavorable prognosis and because they often develop progressive neurological dysfunction that would confuse the assessment of neurological and other adverse events. Patients with a history of CNS or meningeal involvement should be in documented remission by assessing cerebrospinal fluid and contrast-enhanced MRI for at least 90 days before registration; history of active malignancy, other than non-melanoma skin cancer, carcinoma in situ (eg, cervical, bladder, breast); HIV infection; HTLV; individuals with uncontrolled intercurrent disease, among others, existing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, lung abnormalities or psychiatric diseases / social situations that would limit compliance with the requirements of the study; pregnant or lactating women are excluded from this study, as treatment with CAR T cells may be associated with the potential for teratogenic or abortion effects. Fertile women must have a negative serum pregnancy test result. As there is an unknown but possible risk of adverse events in infants secondary to the mother's treatment with CAR T cells, breastfeeding should be discontinued. These possible risks can also be applied to other agents used in this study. Fertile individuals must be willing to use contraceptives from admission to this study and for 4 (four) months after receiving the preparatory regime; evidence of myelodysplasia or cytogenetic abnormality indicative of myelodysplasia in any bone marrow biopsy before the start of treatment; serological status reflecting active hepatitis B or C infection. Patients who test positive for hepatitis B core antibody, hepatitis B surface antigen (HBsAg), or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result prior to admission. (patients with a positive PCR result will be excluded); serious and / or potentially fatal medical conditions; patients with a clinical history of pathology in the relevant central nervous system such as epilepsy, convulsive diseases, paresis, aphasia, severe brain injury, dementia and Parkinson's disease; history of autoimmune disease (such as rheumatoid arthritis, systemic lupus erythematosus) in need of immunosuppressive medication in the last 12 months; history of severe hypersensitivity to one of the agents used in the study; creatinine level below 30 ml / min

Study & Design

• Study Type: Intervention
• Study Design: Not specified