CAR T-cell therapy targeting CD19 for aggressive lymphoma and leukemia

A Phase 1b/2 Multi-center, De-centralized, Dose Selection Study of Autologous CD19-directed Chimeric Antigen Receptor (CAR) T-cells in Patients With Relapsed/Refractory Aggressive Lymphoma or Acute Lymphoblastic Leukemia (ALL)

This study is testing a new type of treatment using modified immune cells to see if it can help people with aggressive lymphoma or leukemia that hasn't responded to other treatments.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 63 (estimated)
• Ages: 2 Years to 70 Years
• Sex: All
• Sponsor: University of Alberta (other)
• Drugs / interventions: blinatumomab, CAR T, chemotherapy, immunotherapy, prednisone, chimeric antigen receptor, cyclophosphamide, fludarabine
• Locations: 6 sites (Calgary, Alberta and 5 other locations)
• Trial ID: NCT03938987 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the use of autologous T-cells modified to express a chimeric antigen receptor (CAR) that targets CD19, a protein found on certain cancer cells. Patients with relapsed or refractory aggressive lymphoma or acute lymphoblastic leukemia (ALL) will undergo lymphodepleting chemotherapy before receiving a single intravenous dose of these engineered T-cells. The trial is structured in two phases: the first phase focuses on determining the optimal dose, while the second phase aims to expand the treatment to a larger group of patients at the identified effective dose.

Who should consider this trial

Good fit: Ideal candidates include patients aged 2 to 70 with relapsed or refractory CD19+ aggressive lymphoma or ALL who have undergone at least two prior systemic therapies.

Not a fit: Patients who are not eligible for this study include those with non-CD19+ tumors or those who have not received prior systemic therapies.

Why it matters

Potential benefit: If successful, this therapy could provide a new treatment option for patients with aggressive forms of lymphoma and leukemia that have not responded to standard therapies.

How similar studies have performed: Other studies utilizing CAR T-cell therapy targeting CD19 have shown promising results, indicating a potential for success in this approach.

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.

Where this trial is running

Calgary, Alberta and 5 other locations

• Foothills Medical Centre — Calgary, Alberta, Canada (NOT_YET_RECRUITING)
• Tom Baker Cancer Centre — Calgary, Alberta, Canada (NOT_YET_RECRUITING)
• Alberta Children's Hospital — Calgary, Alberta, Canada (NOT_YET_RECRUITING)
• Cross Cancer Institute — Edmonton, Alberta, Canada (RECRUITING)
• Stollery Children's Hospital — Edmonton, Alberta, Canada (NOT_YET_RECRUITING)
• University of Alberta Hospital — Edmonton, Alberta, Canada (RECRUITING)

Study contacts

• Principal investigator: Dr. Michael P Chu, MD — Cross Cancer Institute
• Study coordinator: Zack Breckenridge

Conditions: Relapsed Non Hodgkin Lymphoma, Relapsed Adult ALL, Relapsed Pediatric ALL