Clinical trial NCT02846584: a Clinical Research of Sequential CAR-T Bridging HSCT in the Treatment of Relapse/Refractory B-cell Malignancies
Official title: a Clinical Research of Sequential CAR-T Bridging Hematopoietic Stem Cell Transplantation in the Treatment of Relapse/Refractory B-cell Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Lymphoma, Large B-Cell, Diffuse
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma，Malignant
Keywords: CAR T
HSCT
Lead sponsor: Southwest Hospital, China
Sponsor class: OTHER
First posted: 2016-07-27
Enrollment: 100
Sex: ALL
Minimum age (years): 14
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of this study is to explore the sequential therapeutic effect and evaluate the safety of anti-CD19 or anti-CD20 CAR-T cells briging HSCT in the treatment of relapse/refractory B cell malignancies.

Detailed description: The CD19-targeted CAR-T has shown exellent therapeutic efficiency in B cell malignancies,especially in acute lymphocytic leukemia. Recently the anti-CD20 CAR T cells has been used in the treatment of relapsed/refractory DLBCL and exhibited good clinical outcomes.

However, patients treated with CAR-T may face relapse of CD19 or CD20 mutation. Therefore we attempt to maintain and relieve patients by sequential therapy of the HSCT and hope to combine their advantages.

Eligibility criteria: Inclusion Criteria:

1. CD19-expressing or CD20-expressing relapsed or refractory B cell malignancies after at least one standard chemotherapy and one salvage regimen.According to current traditional therapies, there must be no available alternative curative therapies.
2. Patients enrolled must have an evaluated score above 60 with KPS.
3. Expected survival time of patients enrolled is over 3 months.
4. Gender is not limited, age from 14 years to 75 years.
5. 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.
6. Adequate absolute CD3 count estimated need to be assured for obtaining target cell dose based on dosage cohorts.
7. Subjects with the following CNS status are eligible only in the absence of neurologic symptoms suggestive of CNS leukemia, such as cranial nerve palsy: CNS 1, defined as absence of blasts in cerebral spinal fluid (CSF) on cytospin preparation, regardless of the number of WBCs; CNS 2, defined as presence of \< 5/uL WBCs in CSF and cytospin positive for blasts, or \> 5/uL WBCs but negative by Steinherz/Bleyer algorithm CNS3 with marrow disease who has failed salvage systemic and intensive IT chemotherapy (and therefore not eligible for radiation)
8. Patients with isolated CNS relapse will be eligible if they have previously been treated with cranial radiation (at least 1800 cGy).
9. Ability to give informed consent.
10. Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
11. 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.
12. Renal function: Creatinine level of peripheral blood is required no greater than 133umol/L.
13. 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.
14. Patients volunteer to participate in the research.

Exclusion Criteria:

- Subjects meeting any of the following criteria are not eligible for participation in the study:

1. Patients are evaluated below 50 scores with KPS.
2. Evident signs suggesting that patients are potentially allergic to cytokines.
3. Frequent infection history and recent infection is uncontrolled.
4. Patients with concomitant genetic syndrome: patients with Down syndrome, Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome
5. Active acute or chronic graft-versus-host disease (GVHD) or requirement of immunosuppressant medications for GVHD within 4 weeks of enrollment.
6. 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.
7. Pregnancy and nursing females. HIV infection.
8. Active hepatitis B or active hepatitis C.
9. 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.
10. Class III/IV cardiovascular disability according to the New York Heart Association Classification.
11. Patients with a known history or prior diagnosis of other serious immunologic, malignant or inflammatory disease.
12. Other situations we think not eligible for participation in the research.

Primary outcomes:
measure: Overall survival rate of patients treated with anti-CD19 or anti-CD20 CAR T cells
timeFrame: 2 years
Secondary outcomes:
measure: Treatment response rate of anti-CD19 CAR T cell infusion
timeFrame: 4 weeks
measure: Number of patients with adverse events
timeFrame: 2 years
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Southwest Hospital of Third Millitary Medical University
state: Chongqing
Study officials:
affiliation: Southwest Hospital, China
name: Jieping Chen, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References: