High Risk Hematologic Malignancies, Relapsed and/or Refractory Acute Myeloid Leukemia
Conditions
Keywords
CD33, anti-CD33 CAR, leukemia, acute myeloid leukemia, hematologic malignancies
Brief summary
This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of anti-CD33 CAR-T cells in patients with relapsed and/or refractory, high risk hematologic malignancies.
Detailed description
AML is a rapidly progressing blood cancer and treated by high-dose multi-agent chemotherapy potentially followed by hematopoietic stem cell transplantation. Despite such intensive therapies, which are often associated with considerable toxicities and even death, about 60-70% of AML patients still relapse. Furthermore, the five-year survival rate from AML remains at a dismal 27%. AML is composed mostly of CD33+ leukemic blast cells. Therefore, CD33 is a potential good target by CAR T cells.
Interventions
BIOLOGICALanti-CD33 CAR T cells
Anti-CD33 CAR T cells are used to treat patients. Patient will be administered either fresh or thawed CAR T cells by IV injection after receiving lymphodepleting chemotherapy.
Sponsors
iCar Bio Therapeutics
iCell Gene Therapeutics
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
1. Signed written informed consent; Patients volunteer to participate in the clinical trial; 2. Diagnosis is mainly based on the World Health Organization (WHO) 2008; 3. Complete remission cannot be achieved after induction therapy; recurrence occurs after completion remission; the burden of leukemic blasts in the peripheral blood or bone marrow is greater than 5%; 4. Leukemic blast cells express CD33 (CD33 positive by flow cytometry or immunohistochemistry ≥70%); 5. The expected survival period is greater than 12 weeks; 6. ECOG score ≤2; 7. Age 2-60 years old; 8. HGB≥70g/L (can be transfused); 9. Total bilirubin does not exceed 3 times the upper limit of normal value, and AST and ALT do not exceed 5 times the upper limit of normal value.
Exclusion criteria
1. Patients declining to consent for treatment 2. Prior solid organ transplantation 3. One of the following cardiac issues: atrial fibrillation; myocardial infarction within the past 12 months; prolonged QT syndrome or secondary QT prolongation; clinically significant pericardial effusion; cardiac insufficiency NYHA (New York Heart Association) III or IV; 4. History of severe pulmonary dysfunction diseases; 5. Severe infection or persistent infection cannot be effectively controlled; 6. Severe autoimmune disease or congenital immunodeficiency; 7. Active hepatitis; 8. Human immunodeficiency virus (HIV) infection; 9. Clinically significant viral infections, or uncontrollable viral reactivation, including EBV (Epstein-Barr virus).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The number and incidence of adverse events after anti-CD33 CAR infusion. | 1 year, particularly the first 3 months after CAR infusion | Determine the toxicity profile of anti-CD33 CAR T cell therapy including the number, incidence, and severity of symptoms such as cytokine release syndromes and neurotoxicity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Allogeneic hematopoietic stem cell transplantation (HCT) | 42 days after HCT ingraftment | Allogeneic hematopoietic stem cell transplantation (HCT) is performed after anti-CD33 CAR T treatment. The time after HCT engraftment \[time range: 42 days after HCT ingraftemnt\] is calculated from the day of HCT until the absolute neutrophil count (ANC) is greater than 500 / ul for three consecutive days. |
| HCT 100% chymerism time | 2 weeks after HCT | HCT 100% chymerism time |
| The disease response to anti-CD33 CAR T cells | 4 weeks | The disease response to anti-CD33 CAR T cells is evaluated by bone marrow biopsy and aspirate at 1, 2, 3, and 4 weeks. The proportion of subjects receiving anti-CD33 CAR T infusion to 1) morphological remission (blasts \<5%): 2) flow cytometry analysis was blast negative, and 3) molecular biological remission (if applicable). |
| Progress-free survival | one year after HCT | Progress-free survival is measured from the injection of anti-CD33 CAR T cells until the record of disease progression or death due to any reason, whichever comes first. |
| Treatment-related mortality | one year after HCT | Treatment-related mortality calculated from one year after HCT. |
| Overall survival | 1 year after HCT | The time from the start of anti-CD33 CAR T injection to death is determined as the overall survival |
Countries
China
Contacts
Primary ContactKevin Pinz, MS
Outcome results
None listed