Genetically Engineered Cells (CART22 T Cells) for the Treatment of Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia in Pediatric Patients
- Signed informed consent form must be obtained prior to any study procedure. Labs, marrows or other procedures obtained during routine clinical care may be used for eligibility if obtained within the protocol required windows
- Relapsed or refractory B-cell ALL: * 2nd or greater bone marrow (BM) relapse OR * Any marrow relapse after allogeneic hematopoietic stem cell transplantation (HSCT) and >= 6 months from SCT at infusion OR * Any marrow relapse after chimeric antigen receptor (CAR)-modified T cell therapy OR * Refractory disease defined as having not achieved a complete remission (CR) after >= 2 chemotherapy regimens OR * Patients with Ph+ ALL are eligible if they are intolerant to or have failed tyrosine kinase inhibitor therapy OR * Ineligible for allogeneic SCT because of: ** Comorbid disease ** Other contraindications to allogeneic SCT conditioning regimen ** Lack of suitable donor ** Prior SCT ** Declines allogeneic SCT as a therapeutic option after documented discussion, with expected outcomes, about the role of SCT with a bone marrow transplant (BMT) physician not part of the study team * Patients with central nervous system (CNS)3 disease will be eligible if CNS disease is responsive to therapy (at infusion, must meet criteria)
- Documentation of CD22 tumor expression in bone marrow or peripheral blood by flow cytometry at relapse (or a recent marrow in the case of refractory disease). If the patient has received CD22-directed therapy (i.e. inotuzumab), then the marrow should be obtained after this therapy to show CD22 expression
- A serum creatinine based on age/gender as follows: * Age: Maximum Serum Creatinine (mg/dL) * 1 to < 2 years: 0.6 (male and female) * 2 to < 6 years: 0.8 (male and female) * 6 to < 10 years: 1.0 (male and female) * 10 to < 13 years: 1.2 (male and female) * 13 to < 16 years: 1.5 (male), 1.4 (female) * >= 16 years: 1.7 (male), 1.4 (female)
- Alanine aminotransferase (ALT) =< 5 x upper limit of normal range
- Bilirubin =< 2.0 mg/dl
- Must have a minimum level of pulmonary reserve defined as =< grade 1 dyspnea, pulse oxygen > 92% on room air; diffusion capacity of the lung for carbon monoxide (DLCO) >= 40% (corrected for anemia) if pulmonary function tests (PFTs) are clinically appropriate as determined by the treating investigator
- Left ventricle shortening fraction (LVSF) >= 28% or ejection fraction (LVEF) >= 40% confirmed by (echocardiogram) ECHO/multigated acquisition scan (MUGA)
- Evidence of disease by standard morphologic or by minimal residual disease (MRD) criteria. A clinical marrow showing disease may be performed at enrollment or within 12 weeks of enrollment
- Adequate performance status (Lansky or Karnofsky score >= 50)
- Subjects of reproductive potential must agree to use acceptable birth control methods
- Active hepatitis B or active hepatitis C
- Human immunodeficiency virus (HIV) infection
- Active acute or chronic graft-versus-host disease (GVHD) requiring systemic therapy
- Concurrent use of systemic steroids or immunosuppressant medications. Recent or current use of inhaled steroids or physiologic replacement with hydrocortisone is not exclusionary
- CNS3 disease that is progressive on therapy, or with CNS parenchymal lesions that might increase the risk of CNS toxicity
- Pregnant or nursing (lactating) women
- Receipt of a prior investigational study agent within 4 weeks prior to screening visit * Note- patients who have received anti-CD19 CART cells (e.g. CART19/CTL019) on an investigational study where cell infusion occurred greater than 4 weeks before the screening visit are NOT excluded
I. Assess the safety of anti-CD22 scFv TCRz:41BB-CAR lentiviral vector-transduced autologous T-lymphocytes (CART22) in acute lymphoblastic leukemia (ALL) subjects.
I. Evaluate manufacturing feasibility of CART22.
II. Evaluate CART22 efficacy.
III. Characterize CART22 pharmacokinetic (PK) profile.
IV. Evaluate bioactivity of CART22 cells.
Patients receive anti-CD22 scFv TCRz:41BB-CAR lentiviral vector-transduced autologous T-lymphocytes intravenously (IV) over 1-10 minutes on days 1, 2, and 3 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at days 4, 7, 11, 14, 21, and 28, then at months 2, 3, 4, 5, 6, 9, 12, 18 and 24.
Trial Phase Phase I
Trial Type Treatment
Children's Hospital of Philadelphia
Stephan A. Grupp
- Primary ID 15CT055
- Secondary IDs NCI-2019-05330, 15-012219
- Clinicaltrials.gov ID NCT02650414