Background:
CAR (Chimeric Antigen Receptor) T cell therapy is a type of cancer treatment in which a person s T cells (a type of immune cell) are changed in a laboratory to recognize and attack cancer cells. Researchers want to see if this treatment can help people with hairy cell leukemia (HCL).
Objective:
To test whether it is safe to give anti-CD22 CAR T cells to people with HCL.
Eligibility:
Adults ages 18 and older with HCL (classic or variant type) who have already had, are unable to receive, or have refused other standard treatments for their cancer.
Design:
Participants will be screened with the following:
Medical history
Physical exam
Blood and urine tests
Biopsy sample
Electrocardiogram
Echocardiogram
Lung function tests
Imaging scans
Some screening tests will be repeated during the study.
Participants may need to have a catheter placed in a large vein.
Participants will have magnetic resonance imaging of the brain.
Participants will have a neurologic evaluation and fill out questionnaires.
Participants will have leukapheresis. Blood will be removed from the participant. A machine will divide whole blood into red cells, plasma, and lymphocytes. The lymphocytes will be collected. The remaining blood will be returned to the participant.
Participants will get infusions of chemotherapy drugs.
Participants will get an infusion of the anti-CD22 CAR T cells. They will stay at the hospital for 14 days. Then they will have visits twice a week for 1 month.
After treatment, participants will be followed closely for 6 months, and then less frequently for at least 5 years. Then they will have long-term follow-up for 15 years.
* Histologically confirmed diagnosis of HCL or HCLv according to morphological and immunophenotypic criteria of WHO classification [WHO, 2008 revised 2016] of lymphoid neoplasm.
ANC <1/nL,
Hemoglobin <10g/dL,
Platelets<100/nL,
Pregnancy
Participants receiving steroids may be enrolled, provided there has been no increase in dose for at least 1 week prior to starting apheresis;
For radiation therapy: Radiation therapy must have been completed at least 3 weeks prior to enrollment (including CNS radiation), with the exception that there is no time restriction if the volume of bone marrow treated is less than 10% and also the participant has measurable/evaluable disease outside the radiation port.
Other anti-neoplastic investigational agents, or antibody-based therapies currently or within 2 weeks prior to apheresis
Sequential
CD22CART cell infusion
Biological/VaccineThe treatment regimen will consist of lymphodepleting chemotherapy followed by CD22CART infusion: Days -4 to -2: fludarabine 25 mg/m2/dose Day -2: cyclophosphamide 900 mg/m2/dose Day 0: CD22CART infusion (starting at dose level 1 \[DL1\]: 1 x 105 transduced CAR-T cells/kg) on Day 0 participants will be evaluated for response at Day 28 post-CD22CART infusion.
safety and feasibility
Fraction of participants at each dose level who experience a toxicity along with the grades and types of toxicity and which can successfully manufacture the targeted dose number
antitumor effect
The fraction of participants who experience a CR among the 10 evaluable participants treated at the MTD or highest safe dose
expansion and persistence
Measure expansion and persistence of adoptively-transferred anti-CD22-CAR-transduced T-cells in the blood and, where possible, the bone marrow
MRD negative CR
Fraction of HCL participants who achieve MRD negative CR following treatment with anti-CD22-CAR engineered T-cells
duration of response
The time between the initial response to therapy and subsequent disease progression or relapse
progression free-survival
Duration of time from the start of treatment until time of disease relapse from PR, disease progression, or death, whichever occurs first
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