Clinical trial NCT03544021: CART-19 FOR Relapsed/Refractory Acute Lymphoblastic Leukemia （ALL）
Official title: CD19-Targeted CAR-T in Treating Patients With Relapsed/Refractory Acute Lymphoblastic Leukemia （ALL）
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Leukemia, Lymphocytic, Acute
Keywords: Acute Lymphocytic Leukemia
Relapsed
Refractory
Lead sponsor: The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
Sponsor class: OTHER
First posted: 2018-06-01
Enrollment: 10
Sex: ALL
Minimum age (years): 14
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the safety and efficiency of CD19-Targeted CAR-T in Treating Patients with relapsed/refractory acute leukemia.

Detailed description: The relapsed/refractory ALL patients will receive FC (F,Fludarabine，C，Cyclophosphamide) chemotherapy followed by infusion of allogenic or autologous CD19-Targeted CAR-T cells.No graft-versus-host disease (GVHD) prevention will be conducted before or after infusion. Dose-limiting toxicity,incidence of adverse events and disease response will be detected post-infusion.

Eligibility criteria: Inclusion Criteria:

* CD19-expressing ALL must be assured and must be relapsed or refractory disease. According to current traditional therapies, there must be no available alternative curative therapies and subjects must be either ineligible for allogeneic stem cell transplant (SCT), have refused SCT, or have disease activity that prohibits SCT at this time.
* Estimated life expectancy ≥ 12 weeks (according to investigator's judgment)
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
* CD19 expression of the malignant cells must be detected by immunohistochemistry or by flow cytometry
* Patients must have measurable or evaluable disease at the time of enrollment, which may include any evidence of disease including minimal residual disease detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
* Patients must have an healthy donor for T cells.
* Cardiac function: Left ventricular ejection fraction greater than or equal to 40% by MUGA or cardiac MRI, or fractional shortening greater than or equal to 28% by ECHO or left ventricular ejection fraction greater than or equal to 50% by ECHO.
* Renal function: Creatinine level of peripheral blood is required no greater than 133umol/L.
* Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
* Patients with history of allogeneic stem cell transplantation are eligible if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to enrollment.
* Ability to give informed consent.

Exclusion Criteria:

* Evident signs suggesting that patients are potentially allergic to cytokines.
* Frequent infection history and recent infection is uncontrolled.
* Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome.
* Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
* Concurrent use of systemic steroids or chronic use of immunosuppressant medications. Recent or current use of inhaled steroids is not exclusionary. For additional details regarding use of steroid and immunosuppressant medications.
* Pregnancy and nursing females.
* HIV infection.
* Active hepatitis B or active hepatitis C.
* Participation in a prior investigational study within 4 weeks prior to enrollment or longer if required by local regulation. Participation in non-therapeutic research studies is allowed.
* Patients with a known history or prior diagnosis of other serious immunologic, malignant or inflammatory disease.
* Other situations we think not eligible for participation in the research.

Primary outcomes:
measure: Dose-limiting toxicity
timeFrame: 28 days
measure: Incidence of adverse events as assessed
timeFrame: 3 months
measure: Disease response (CR or CRi)
timeFrame: 3 months
Secondary outcomes:
measure: Engraftment of transferred CD19+ CAR T cells
timeFrame: 28 days
measure: CAR19-specific antibody level
timeFrame: 6 months
measure: Duration of response
timeFrame: 1year
measure: Progression Free Survival
timeFrame: 1year
measure: Survival
timeFrame: 1year
Other outcomes:
Locations:
city: Beijing
country: China
facility: 307 Hospital of PLA
state: Beijing
Study officials:
affiliation: 307 Hospital of PLA
name: HUISHENG AI
role: STUDY_CHAIR
References: