A Phase 1/2 Study of CAT-8015 in Adult Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

Inclusion Criteria

Inclusion Criteria

- Subjects must be at least 18 years of age or older

- Written informed consent and HIPAA authorization

- Subjects must have histologically-confirmed B-cell CLL, including SLL, DLBCL, MCL, or
FL.

- B-cell NHL (DLBCL, FL, MCL):

- Have previous confirmation of B-cell NHL

- Subjects with DLBCL or MCL, must have relapsed or refractory disease after at
least one prior regimen containing rituximab, either alone or in combination,
and be ineligible for any available standard line of therapy known to be
life-prolonging or life-saving.

- Subjects with FL, must have relapsed or refractory disease after at least two
prior regimens, one of which included rituximab, either alone or in combination,
and be ineligible for any available standard line of therapy known to be
life-prolonging or life-saving.

- Have measurable disease (at least one lesion ≥ 20 mm in one dimension or ≥
15 mm in two dimensions as measured by conventional or high resolution [spiral]
computed tomography (CT)

- Not be a candidate for a hematopoietic stem cell (HSC) or bone marrow (BM)
transplant

- B-cell CLL:

- Have previous confirmation of B-cell CLL with a characteristic immunophenotype
by flow cytometry

- Have relapsed or refractory disease after at least 2 prior lines of treatment,
at least 1 of which must have contained rituximab and be ineligible for any
available standard line of therapy known to be life-prolonging or life-saving

- Not be a candidate for an HSC or BM transplant

- Have symptomatic disease that requires treatment

- Karnofsky Performance Status ≥ 70

- Life expectancy of ≥ 12 weeks

- Toxicities from previous cancer therapies must have recovered to Grade < 2.

- Adequate hematological function defined as:

- Hemoglobin ≥ 9 g/dL

- Absolute neutrophil count ≥ 1500/mm3

- Platelet count ≥ 75,000/mm3 ((except for CLL subjects with evidence of bone
marrow disease, who must have a platelet count ≥ 50,000/mm3)

- Adequate organ function defined as follows:

- AST and ALT ≤ 2 × institutional ULN, except in the case of liver involvement ≤ 5
× ULN

- Bilirubin ≤ 1.5 × ULN, except in the case of subjects with documented Gilbert's
disease ≤ 2.5 × ULN

- Creatinine clearance ≥ 50 mL/min as determined by the Cockcroft-Gault equation
or by 24-hour urine collection for determination of creatinine clearance

- PT-INR/ PTT ≤ 1.5 × ULN, or for patients on anticoagulation therapy, status within
therapeutic range

- Women of non-child-bearing potential or using effective contraception

- Male subjects with partners of child-bearing potential must be surgically sterile or
use a contraceptive method

- For the expansion phase only, subjects with DLBCL, FL, and MCL only, disease must be
evaluable by the International Working Group criteria (Cheson et al, 2007).

Exclusion Criteria

Any of the following excludes the subject from participation in the study:

- Any available standard line of therapy known to be life-prolonging or life-saving

- Any concurrent chemotherapy, radiotherapy, immunotherapy, biologic, or hormonal
therapy for treatment of cancer

- For CLL patients only,rapidly progressive disease that in the estimation of the
investigator and sponsor would compromise ability to complete study therapy

- History of allergy or reaction to any component of the CAT-8015 formulation

- Receipt of any chemotherapy or small molecule targeted therapy regimens within 6
weeks

- Receipt of any biological- or immunological-based therapies for leukemia or lymphoma
within 6 weeks

- Prior radiation therapy will not be excluded, providing the volume of bone marrow
treated is less than 25%.

- Any history of prior pseudomonas-exotoxin (PE) immunotoxin administration including
CAT-8015, CAT-3888, or LMB-2 (anti-CD25 immunotoxin)

- History of other invasive malignancy within 5 years, with some exceptions

- Evidence of significant active infection requiring antimicrobial, antifungal,
antiparasitic or antiviral therapy or for which other supportive care is given

- Autologous stem cell transplantation within 6 months prior to study entry

- Allogenic stem cell transplantation or any other organ transplant

- HIV-positive or AIDS

- Hepatitis B or hepatitis C infection as defined by seropositive for hepatitis B
(HBsAg) or hepatitis C and elevated liver transaminases

- Use of immunosuppressive medication other than steroids within 7 days

- Use of systemic steroids within 7 days before the first dose of CAT-8015 (inhaled and
topical corticosteroids are permitted). Subjects may take replacement doses of
steroids (defined as ≤ 30 mg/day hydrocortisone or the equivalent) if on a stable
dose for at least 2 weeks prior to the first dose of CAT-8015.

- Documented current central nervous system involvement by leukemia or lymphoma

- Pregnancy or lactation

- Other severe, concurrent diseases

- Concurrent enrollment in another clinical study