Relapsed/Refractory, High Risk Hematologic Malignancies, T-ALL/Lymphoma
Conditions
Keywords
CD7, CD7CAR, leukemia, acute lymphoblastic leukemia/lymphoma, hematologic malignancies
Brief summary
This is a phase I, interventional, single arm, open label, treatment study to evaluate the safety and tolerability of CD7 CAR-T cells in patients with relapsed and/or refractory, high risk hematologic malignancies.
Detailed description
T-acute lymphoblast leukemia (T-ALL) accounts for 15-20% of all ALL cases. It is a neoplastic lymphoid leukemia characterized by the proliferation of immature precursor T cells. T-ALL is a highly aggressive tumor. Adults need intensive chemotherapy, and the cure rate is \<50%, even with stem cell transplantation. The prognosis is also very poor. The combined chemotherapy has significantly improved the prognosis of T-acute lymphoblast leukemia/lymphoma. However, once the disease appears to be relapsed/refractory, there is limited treatment options, and the overall prognosis is extremely poor. Therefore, exploring safe and effective treatments is a critical unmet medical need. Since 95% of T-ALLs express CD7, this might provide an effective targeting approach for the vast majority of T-ALL cases.
Interventions
BIOLOGICALCD7CAR T cells
CD7 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
Intervention model description
CD7 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.
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 CD7 (CD7 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 CD7 CAR infusion. | Up to 3 months | Evaluation all possible adverse reactions, including the number, incidence, and severity of symptoms such as cytokine release syndromes and neurotoxicity within 3 months after CAR infusion |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease response to CD7 CAR T cells | Up to 1 year | The disease response to CD7 CAR T cells is evaluated by bone marrow biopsy and aspirate within 1 years after CAR infusion. The proportion of subjects receiving CD7 CAR T infusion to 1) morphological remission (blasts \<5%): 2) flow cytometry analysis was blast negative, and 3) molecular biological remission (if applicable). |
| Evaluation of curative effects | Up to 1 year | Evaluation of curative effects within 1 year including 1)completion remission (CR), 2) complete remission with incomplete recovery of blood cells (CRi), 3) minimal residual disease positive (MRD+), 4)minimal residual disease negative (MRD-), and 4) disease recurrence or progression |
| Overall survival | Up to 1 year | Overall survival {1 year after CAR infusion\] . The time from the start of CD7 CAR T injection to death is determined as the overall survival |
Countries
China
Contacts
Primary ContactKevin Pinz, MS
Outcome results
None listed