B-cell leukemias and lymphomas are cancers that are often difficult to treat. The primary
objective of this study is to determine the ability to take a patient's own cells (T
lymphocytes) and grow them in the laboratory with the CD19/CD22-CAR receptor gene through a
process called 'lentiviral transduction (also considered gene therapy) and growing them to
large numbers to use as a treatment for hematologic cancers in children and young adults..
Researchers want to see if giving modified CD19/CD22-CAR T cells to people with these cancers
can attack cancer cells. In addition, the safety of giving these gene modified cells to
humans will be tested at different cell doses. Additional objectives are to determine if this
therapy can cause regression of B cell cancers and to measure if the gene modified cells
survive in patients blood.
To study the safety and effects of giving CD19/CD22-CAR T cells to children and young adults
with B-cell cancer.
People ages 3 35 with certain cancers that have not been cured by standard therapy. Their
cancer tissue must express the CD19 protein.
A sample of participants blood or bone marrow will be sent to NIH and tested for leukemia.
Participants will be screened with:
Urine and blood tests (including for HIV)
Heart and eye tests
Neurologic assessment and symptom checklist.
Scans, bone marrow biopsy, and/or spinal tap
Some participants will have lung tests.
Participants will repeat these tests throughout the study and follow-up.
Participants will have leukapheresis. Blood will be drawn from a plastic tube (IV) or needle
in one arm then go through a machine that removes lymphocytes. The remaining blood will be
returned to the participant s other arm.
Participants will stay in the hospital about 2 weeks. There they will get:
Two chemotherapy drugs by IV
Their changed cells by IV
Standard drugs for side effects
Participants will have frequent follow-up visits for 1 year, then 5 visits for the next 4
years. Then they will answer questions and have blood tests every year for 15 years.
Acute lymphoblastic leukemia (ALL) accounts for approximately 25% of childhood cancer.
Survival rates have improved, but outcomes for some subgroups, including infants and
young adults remain poor, and survival for patients who relapse is < 50%, despite
allogeneic stem cell transplant following second remission.
CD19 immune escape has been observed by several groups following CD19-CAR therapy for
B-ALL. Investigation of this phenomenon reveals a complex biology responsible for loss
or downregulation of CD19 expression observed in these cases.
Sequential therapy using CD22-CARs to treat CD19 dim/lo escape is associated with rapid
development of resistance due to CD22 downregulation. This trial will test whether
simultaneous targeting of CD19 and CD22 using a novel bivalent CD19/22-CAR is safe and
-Assess the safety of administering escalating doses of autologous CD19/CD22-CAR engineered T
cells that meet established release specifications in children and young adults with
CD19+CD22+ B cell ALL or lymphoma following a cyclophosphamide/fludarabine conditioning
-Patients between greater than or equal to 3 years and less than or equal to 35 years of age,
with CD19+/CD22+ B cell ALL or lymphoma who have relapsed or have refractory disease after at
least one standard chemotherapy regimen and one salvage regimen, with no alternative curative
options who meet standard Phase I eligibility criteria.
Phase I, 3 + 3 dose escalation design using the following dose levels: -1: 1 x 10^5
transduced T cells/kg (+/- 20%); 1: 3 x 10^5 transduced T cells/kg (+/- 20%); 2: 1 x
10^6 transduced T cells/kg; and 3: 3 x 10^6 transduced T cells/kg (+/- 20%); 4: 1 x 10^7
transduced T cells/kg (+/- 20%).
Patients will receive a lymphodepleting preparative regimen of fludarabine (25 mg/m^2/d
x 3 on Days -4, -3, -2) and cyclophosphamide (900 mg/m^2/d x 1 on Day -2) followed by
infusion of CD19/CD22-CAR T-cells on D0. Patients who are CAR pre-treated (with
exception for those with an interval HSCT) will receive increased lymphodepleting
preparative regimen of fludarabine (30 mg/m^2/d x 4 on Days -5, -4, -3, -2) and
cyclophosphamide (600 mg/m^2/d x 2 on Days -3, -2) followed by infusion of CD19/CD22-CAR
T-cells on D0.
Patients will be evaluated sequentially for toxicity, antitumor effects, CAR expansion
and persistence, as well as research correlatives.
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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