Clinical trial NCT02794961: CD22 Targeting CAR-T Therapy Against B Cell Hematological Malignancies
Official title: Application of Humanized Anti-CD22 Antibody in CAR-T Therapy of B Cell Hematological Malignancies
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Recurrent or Refractory B Cell Malignancy
Lead sponsor: Xuzhou Medical University
Sponsor class: OTHER
Collaborators: name: iCarTAB BioMed Inc.
First posted: 2016-06-09
Enrollment: 10
Sex: ALL
Minimum age (years): 4
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: CD19 expression on B cell frequently lost after CD19-targeting CAR-T therapy. In present study, we construct a CD22-targeting chimeric antigen receptor to overcome this issue.

Detailed description: CD19 is an ideal target with great potential for treating B-cell-derived hematological malignancies. Although the complete remission rate is as high as 93% by using CD19-targeting CAR-T technology, approximately 60% patients will have recurrent disease. Among all the recurrent patients, two thirds is revealed to loss their CD19 expression on B cell surface. For overcoming this issue, we establish a new chimeric antigen receptor containing humanized single chain antibody sequence to target CD22 molecule on B cells.

Eligibility criteria: Inclusion Criteria:

* Greater than four years of age
* Survival time\>12 weeks
* B cell hematological malignancies by pathological examination
* Chemotherapy failure or recurrent B cell malignancy
* Creatinine\< 2.5mg/dl
* Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase\< 3 fold of normal level
* Bilirubin\<2.0mg/dl
* Karnofsky Performance Status\>50% at the time of screening
* Adequate pulmonary, renal, hepatic, and cardiac function
* Fail in autologous or allogenic haemopoietic stem cell transplantation
* Free of leukocytes removal contraindications
* Voluntarily join CAR-T clinical trial
* Understand and sign written informed consent

Exclusion Criteria:

* Pregnant or nursing women
* Active hepatitis B, active hepatitis C, or any human immunodeficiency virus (HIV) infection at the time of screening
* Feasibility assessment proves that the efficiency of transduction of lymphocyte is below 10% or the lymphocyte cannot be propagated.
* Abnormal vital signs
* Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2
* General infection or local severe infection, or other infection that is not controlled
* Dysfunction in lung, heart, kidney and brain
* Severe autoimmune diseases
* Other symptoms that are not applicable for CAR-T

Primary outcomes:
measure: Complete remission rate
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Xuzhou
country: China
facility: Affiliated hospital of Xuzhou medical college
state: Jiangsu
Study officials:
affiliation: Xuzhou Medical University
name: KaiLin Xu, MD. Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Haso W, Lee DW, Shah NN, Stetler-Stevenson M, Yuan CM, Pastan IH, Dimitrov DS, Morgan RA, FitzGerald DJ, Barrett DM, Wayne AS, Mackall CL, Orentas RJ. Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia. Blood. 2013 Feb 14;121(7):1165-74. doi: 10.1182/blood-2012-06-438002. Epub 2012 Dec 14.