Anti-CD19, Dual Co-stimulatory (4-1BB, CD3ζ) Chimeric Antigen Receptor T-cells in Patients With Relapsed/Refractory Aggressive Lymphoma or Acute Lymphoblastic Leukemia (ALL)

Launched by UNIVERSITY OF ALBERTA · May 2, 2019

Keywords

ClinConnect Summary

This clinical trial is looking at a new treatment for patients with relapsed or hard-to-treat aggressive lymphoma or acute lymphoblastic leukemia (ALL), which are types of blood cancers. The researchers are testing a special type of immune cell called CAR T-cells that are designed to target a protein called CD19 found on cancer cells. This treatment involves collecting some of the patient's own immune cells, modifying them in the lab to help them fight the cancer better, and then reintroducing them into the patient's body.

To be eligible for the trial, patients need to be between the ages of 2 and 70 and have had at least two previous treatments for their cancer without success. They should also have a confirmed diagnosis of CD19+ lymphoma or ALL and have measurable disease. It's important that potential participants are healthy enough to undergo the treatment and can commit to following the study procedures. If you or a loved one are considering this trial, it offers a chance to receive an innovative therapy that may help when other treatments have not worked.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Have given written informed consent prior to any study-specific procedures; children (defined as 17 years of age or less) require guardian consent.
• • 2. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2; or Karnofsky \> 50%.
• • 3. Age of 2 to 70 years at time of screening.
• • 4. A histologically or cytologically documented, CD19+ non-hodgkin's lymphoma or ALL.
• • 5. At least 1 measurable lesion or FDG-avid disease by positron-emission tomography/computed tomography (PET/CT) for lymphoma patients; quantifiable evidence of ALL in either peripheral blood or bone marrow aspirate.
• • 6. Tumor tissue (archival or recent acquisition) must be available for correlative laboratory studies (such as immunohistochemistry, and others).
• • 7. At least 2 prior systemic therapies and patient must not be eligible for potentially curative standard-of-care therapy.
• • 8. Adequate renal function (defined as Cockroft-Gault creatinine clearance \> 50 mL/min) and hepatic function (total bilirubin \< 1.5x ULN; and AST/ALT \< 3x ULN) unless directly related to malignant disease being treated for on study as demonstrated either by PET/CT imaging or by biopsy and histopathologic confirmation.
• • 9. For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of \< 1% per year during the treatment period and for at least 90 days after the last dose of study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.
• • 10. Male participants should agree to not donate sperm during study period (i.e. up to 2 years following CAR T-cell administration).
• • 11. Male participants with reproductive potential must agree to use medical approved contraceptives during the study and for 90 days following the last dose of study treatment.
• • 12. Are reliable and willing to make themselves available for the duration of the study, and are willing to follow study procedures.
• Exclusion Criteria:
• • 1. Prior treatment with immunotherapy directly targeting T-cells (except anti-thymocyte globulin \[ATG\]), CD19-directed antibody-based therapies (except blinatumomab), or other gene therapy products.
• • 2. Received any investigational drug/anti-cancer therapy within 30 days.
• • 3. Concurrent participation in another therapeutic clinical trial.
• • 4. Therapeutic doses of corticosteroids (defined as \> 20 mg/day prednisone or equivalent) within 7 days prior to blood collection for CAR T-cell product manufacture.
• • 5. Donor lymphocyte infusion (DLI) within 4 weeks prior to leukapheresis.
• • 6. Salvage or debulking chemotherapy within 1 week prior to blood collection for CAR T-cell product manufacture.
• • 7. Prior central nervous system (CNS) involvement.
• • 8. Unresolved acute toxicity of National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.03 Grade \>1 (or baseline, whichever is greater) from prior anticancer therapy. Alopecia and other nonacute toxicities are acceptable.
• • 9. An uncontrolled intercurrent illness including but not limited to ongoing or active infection (including fever within 48 hours of screening), symptomatic congestive heart failure (i.e., New York Heart Association \[NYHA\] Class 3 or 4), unstable angina pectoris, clinically significant and uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• • 10. Major surgical procedure within 30 days.
• • 11. Known history of human immunodeficiency virus (HIV) or active infection requiring therapy, or positive tests for hepatitis B surface antigen or hepatitis C ribonucleic acid (RNA).
• • 12. Any vaccination against infectious diseases (e.g., influenza, varicella) within 4 weeks (28 days) of initiation of study treatment.
• • 13. A woman who is pregnant or breastfeeding.