Retreatment Protocol for BL22 Immunotherapy in Relapsed or Refractory Hairy Cell Leukemia
Condition: Hairy Cell Leukemia
MeSH terms: Leukemia; Leukemia, Hairy Cell
Intervention: BL22 (CAT-3888)
Intervention description: 30 micrograms/kg intravenous over 30 minutes every other day (QOD) on days 1, 3, 5, of a 4 week cycle (at least 26 days) for a maximum of 16 cycles or until they become ineligible.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: BL22 in HCL after Immunotoxin; Hairy Cell Leukemia; Leukemia

Summary:

      BL22 is a type of protein that scientists have created to interact with certain cancer cells.
      Experiments have shown that BL22 can bind with cancer cells that have a particular kind of
      protein (called CD22 ) on their surface, and can kill those cells. CD22 is present on certain
      types of hairy cell leukemia (HCL) cancer cells, and researchers have been working on
      treatments that will use BL22 and other related proteins to interact with and kill these
      kinds of cancer cells. The primary purpose of this study will be to provide access to and
      treatment with BL22 for patients who have HCL in order to determine their response to the
      treatment. In addition, the study will assess potential side effects of BL22 and examine why
      some patients respond better than others to treatment with BL22 and related therapies.

      This study will include about 21 to 25 adults who have been diagnosed with forms of HCL that
      have not responded well to standard treatments such as surgery, chemotherapy, or radiation
      therapy. These adults also will have received anti-CD22 therapies before, potentially
      including treatments with BL22, and have not developed immunity or resistance to these
      treatments.

      Prior to the study, patients will undergo a 1- to 2-week screening period to assess their
      eligibility for treatment. Eligible patients will participate in the study for up to 16
      cycles of treatment, with each cycle lasting approximately 4 weeks. For each cycle, patients
      will receive 1 prescribed dose of BL22 every other day for a total of 3 doses per cycle, and
      will be assessed after every cycle to evaluate the success of the treatment. During the
      evaluation visits, patients will be required to have a brief physical examination, give blood
      and urine samples for testing, and undergo other tests as need to check heart and kidney
      function and assess the state of the leukemia. Patients who agree will give additional blood,
      urine, or bone marrow samples for future research purposes.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

        One of the following:

          1. Patients who previously received CAT-3888 and did not have unacceptable toxicity

          2. Patients who received CAT 8015 in study CAT 8015-1001 and have progression of disease
             or relapse. These patients must be considered off-study for CAT-8015 protocol
             specified follow-up

        Patient must have histopathological evidence of HCL as confirmed by the Laboratory of
        Pathology, NCI.

        At least one of the following indications for treatment:

          1. Neutropenia (absolute neutrophil count (ANC) less than 1000 cells/microL).

          2. Anemia (hemoglobin (Hgb) less than 10 g/dL).

          3. Thrombocytopenia (platelet (Plt) less than 100,000/microL).

          4. Absolute lymphocyte count of greater than 5000 cells/microL

          5. Symptomatic splenomegaly.

          6. Enlarging lymph nodes greater than 2cm.

        Patient must have had at least 2 prior systemic therapies. There must have been at least 2
        prior courses of purine analog, or 1 if the response to this course lasted less than 2
        years, or if the patient had unacceptable toxicity to purine analog.

        Patient must have Eastern Cooperative Oncology Group (ECOG) performance status of 0-2,
        unless due to potentially reversible active uncontrolled infection.

        Patient must be greater than or equal to 18 years old.

        Patient can understand and give informed consent.

        Patient must have adequate liver and renal function, as defined by the following criteria:

          1. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) less than or equal
             to 2.5-times the upper limits of normal.

          2. Albumin greater than or equal to 3.0 g/dL.

          3. Total bilirubin less than or equal to 2.2 mg/dL.

          4. Creatinine less than or equal to 1.4 mg/dL or creatinine clearance greater than or
             equal to 50 mL/min.

        Patient must agree to using adequate contraception (hormonal or barrier method of birth
        control; abstinence) prior to study entry and for the duration of the study.

        EXCLUSION CRITERIA:

        Patients who are pregnant or nursing. A negative pregnancy test (urine or serum) must be
        documented within one week prior to starting BL22 in women of child-bearing potential.

        Patient has developed antibody titer that neutralizes greater than 75% of the activity of 1
        microg/mL of BL22 using a bioassay.

        Patients who had systemic cytotoxic chemotherapy, immunotherapy, recombinant anti-CD22
        immunotoxin (ie, CAT-8015, BL22, or LMB-2) or systemic steroid (with the exception of
        stable doses of Prednisone less than or equal to 20 mg/day) treatment within 4 weeks of
        enrollment. Patients receiving a limited number of doses (less than 5) of steroid for
        non-treatment reasons (eg, allergy prophylaxis connected with medical testing) may not
        receive any steroid within one week of enrollment and may not have had any evidence of
        disease response to steroid. Subjects who are receiving steroids for other conditions
        (e.g., autoimmune disorders) are eligible, as long as there is no increase in the dose or
        change in steroid type within 1 week of treatment. Subjects who are using a chronic steroid
        must wait for 4 weeks before starting the trial.

        Patient had monoclonal antibody therapy (with the exception of BL22 or CAT-8015 or LMB-2)
        within 4 weeks of enrollment.

        Patient is receiving any other investigational agent.

        Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive
        heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social
        situations that would limit compliance with study requirements.

        Patients who discontinued from CAT-8015 or BL22 studies due to toxicity or dose-limiting
        toxicity.

        Dose limiting toxicity to CAT-8015