Clinical trial NCT04572308: Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells
Official title: Cell Therapy for CD7 Positive T-cell Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma Using CD7-Specific CAR-T Cells
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: T-cell Acute Lymphoblastic Leukemia/Lymphoma
Keywords: T-ALL，T-LBL , CD7，CAR-T
Lead sponsor: Hebei Senlang Biotechnology Inc., Ltd.
Sponsor class: INDUSTRY
First posted: 2020-10-01
Enrollment: 20
Sex: ALL
Minimum age (years): 2
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is an open, single-arm, clinical study to evaluate efficacy and safety of anti CD7 CAR-T cell in the treatment of relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL) and lymphoblastic lymphoma (TLBL).

Detailed description: The CARs consist of an anti-CD7 single-chain variable fragment（scFv）, a portion of the human CD137（4-1BB） molecule, and the intracellular component of the human CD3ζ molecule. Prior to CAR-T cell infusion, the patients will be subjected to preconditioning treatment. After CAR-T cell infusion, the patients will be evaluated for adverse reactions and efficacy.

The Main research objectives:

To evaluate the safety and efficacy of CD7 CAR-T cells in patients with relapsed or refractory T-ALL/LBL

The Secondary research objectives:

To investigate the cytokinetic characteristics of CD7 CAR-T cells in patients with relapsed or refractory T-ALL/LBL

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of refractory or relapsed T-cell acute lymphoblastic leukemia (T-ALL) or lymphoblastic lymphoma (T-LBL) according to the NCCN 2019.V2 Guideline. Refractory T-ALL is defined as a patient who has failed to achieve complete remission after induction therapy. Relapsed T-ALL is defined as the reappearance of blasts (5%) in either peripheral blood or bone marrow. Patients whose tumor burden \>5% blasts, or who have persistent positive minimal residual disease (MRD), or have reappearance of extramedullary lesions are also considered eligible.
2. CD7-positive tumor (≥70% CD7 positive blasts by flow cytometry or immunohistochemistry (tissue) assessed by a CLIA certified Flow Cytometry/Pathology laboratory). tumors burden \>5%,or MRD+， or new extramedullary lesions reappeared.
3. Life expectancy greater than 12 weeks
4. KPS or Lansky score≥60
5. HGB≥70g/L
6. oxygen saturation of blood\>90%
7. Total bilirubin (TBil)≤3 × upper limit normal, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal
8. Informed consent explained to, understood by and signed by patient/guardian.

Exclusion Criteria:

1. Any of the following cardiac criteria: Atrial fibrillation/flutter; Myocardial infarction within the last 12 months; Prolonged QT syndrome or secondary prolonged QT, per investigator discretion. Cardiac echocardiography with LVSF (left ventricular shortening fraction)\<30% or LVEF(left ventricular ejection fraction)\<50%; or clinically significant pericardial effusion. Cardiac dysfunction NYHA(New York Heart Association) III or IV (Confirmation of absence of these conditions on echocardiogram within 12 months of treatment)
2. Has an active GvHD;
3. Has a history of severe pulmonary function damaging;
4. With other tumors which is/are in advanced malignant and has/have systemic metastasis;
5. Severe or persistent infection that cannot be effectively controlled；
6. Presence of severe autoimmune diseases or immunodeficiency disease;
7. Patients with active hepatitis B or hepatitis C(\[HBVDNA+\]or \[HCVRNA+\]);
8. Patients with HIV infection or syphilis infection;
9. Has a history of serious allergies to biological products (including antibiotics);
10. Clinically significant viral infection or uncontrolled viral reactivation of EBV(Epstein-Barr virus), CMV(cytomegalovirus), ADV(adenovirus), BK-virus, or HHV(human herpesvirus)-6.
11. Presence of any symtomatic CNS disorder such as an uncontrolled seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement;
12. Received allogeneic hematopoietic stem cell transplantation within 6 months;
13. Being pregnant and lactating or having pregnancy within 12 months;
14. Any situations that the researchers believe will increase the risks for the subject or affect the results of the study.

Primary outcomes:
measure: Safety: Incidence and severity of adverse events
timeFrame: First 1 month post CAR-T cells infusion
measure: Efficacy: Remission Rate
timeFrame: 3 months post CAR-T cells infusion
Secondary outcomes:
measure: duration of response (DOR)
timeFrame: 24 months post CAR-T cells infusion
measure: Efficacy: progression-free survival (PFS)
timeFrame: 24 months post CAR-T cells infusion
measure: CAR-T proliferation
timeFrame: 3 months post CAR-T cells infusion
measure: CAR-T proliferation
timeFrame: 3 months post CAR-T cells infusion
measure: Cytokine release
timeFrame: First 1 month post CAR-T cells infusion
measure: Pharmacokinetics (PK) indicators:
timeFrame: Long time
measure: Pharmacodynamic (PD) indicators:
timeFrame: First 1 month post CAR-T cells infusion
Other outcomes:
Locations:
city: Yanda
country: China
facility: Hebei yanda Ludaopei Hospital
state: Hebei
Study officials:
References: