Phase I Study of Anti-CD22 Chimeric Receptor T Cells in Patients With Relapsed/Refractory Hairy Cell Leukemia and Variant

This is an interventional treatment trial for Hairy Cell Leukemia focused on measuring CD-22 Expressing Tumor, Chimeric Antigen Receptor, Adoptive Immunotherapy Read More

• INCLUSION CRITERIA:

  1. Histologically confirmed diagnosis of HCL or HCLv according to morphological and immunophenotypic criteria of WHO classification [WHO, 2008 revised 2016] of lymphoid neoplasm. Participants should have any of the following indications for therapy:

     • Absolute neutrophil count (ANC) <1/nL,
     • Hemoglobin <10g/dL,
     • Platelets<100/nL,
     • Symptomatic splenomegaly,
     • Enlarging HCL mass or bone lesion > 2cm in short axis,
     • HCL count >5/nL,
     • HCLv count doubling time <3 months,
     • Increasing lytic or blastic bone lesions

     Participants who have eligible blood counts within 4 weeks from the initiation of study will not be considered ineligible if subsequent blood counts prior to enrollment fluctuate and become ineligible up until the time of enrollment

  2. HCL/HCLv, after prior treatment with, ineligible for, refusal of, or inability to obtain 1) Rituximab given concurrently with or sequentially after purine analog, 2) moxetumomab pasudotox-tdft, and 3) BRAF-inhibition.
  3. CD22 expression must be detected on greater than 80% of malignant cells by flow cytometry.
  4. Participants 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 or immunohistochemistry
  5. Age >18 years
  6. ECOG performance <2 (Karnofsky >60%), participants are exempt from this criterion if poor performance status is related to HCL

  7. Participants must have adequate organ function as defined below: Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met. If participants exhibit minor lab abnormalities that are determined to be related

     to HCL (not therapy-related), then those participants will be allowed to participate

     • Total bilirubin less than or equal to 3 ULN, unless consistent with Gilbert s (ratio between total and direct bilirubin > 5)
     • AST and ALT less than or equal to 3x upper limit of normal (ULN)
     • Alkaline phosphatase < 2.5 ULN
     • Serum creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 mL/min/1.73 m^2 for participants with creatinine levels above institutional normal calculated using eGFR or measured
     • Serum albumin > 2 g/dL
     • Prothrombin time (PT)/International Normalized Ratio < 2.5x ULN (If on warfarin, PT/INR < 3.5x ULN; If on any other anticoagulation, Prothrombin time (PT) < 2.5x ULN
     • Fibrinogen greater than or equal to 0.5x lower limit of normal
  8. Subjects with CNS disease are eligible, with exceptions
  9. Participants with history of allogeneic stem cell transplantation are eligible if at least 100 days post-transplant, if there is no evidence of active GVHD and no longer taking immunosuppressive agents for at least 30 days prior to enrollment
  10. Participants of child-bearing or child-fathering potential must use effective contraception from the time of enrollment on this study and for four months after receiving the preparative regimen as agents used in this study are teratogenic.
  11. Ability of subject to understand and the willingness to sign a written informed consent document.

EXCLUSION CRITERIA:

1. Pregnant or breast-feeding females

2. Systemic chemotherapy, immunotherapy, or radiation therapy less than or equal to 2 weeks prior to apheresis; with the following exception:

   • Subjects 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 subject has measurable/evaluable disease outside the radiation port.
3. Other anti-neoplastic investigational agents, or antibody based therapies currently or within 2 weeks prior to apheresis
4. Subjects taking warfarin
5. Prior CAR therapy within 30 days prior to apheresis or prior CAR therapy at any time with evidence for persistence of CAR T-cells in blood samples (circulating levels of genetically modified cells of greater than or equal to 5% by flow cytometry)

6. HIV/HBV/HCV Infection:

   • Seropositive for HIV antibody. (Participants with HIV are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy in the future should study results indicate effectiveness.)
   • Seropositive for hepatitis C or positive for Hepatitis B surface antigen (HbsAG). Participants who convert to negative will not be excluded for history of positive test.
7. Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris, cardiac arrhythmia, asthma, chronic obstructive pulmonary disease, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject
8. Second malignancy other than in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least two years previously and subject is in remission
9. History of severe, immediate hypersensitivity reaction attributed to compounds of similar chemical or biologic composition to any agents used in study or in the manufacturing of the cells (i.e., gentamicin)