Phase I Dose Escalation Study of IMMU-114 in Relapsed or Refractory NHL and CLL

A Phase I Dose Escalation Study of Immunotherapy With IMMU-114 in Patients With Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

IMMU-114 will be studied at different dose schedules and dose levels in order to assess the highest dose safely tolerated. IMMU-114 will be administered subcutaneously (under the skin). IMMU-114 will be given 1-2 times weekly for 3 weeks followed by one week of rest. This is considered one cycle. Treatment cycles will be repeated until toxicity or worsening of disease.

Inclusion Criteria:

• Each patient with CLL/SLL must meet all of the following inclusion criteria to be enrolled on the study:
• Patients must have met the diagnostic criteria for CLL/SLL according to the IWCLL 2008 [13] or WHO Guidelines at some point during their disease course:
• Patients with SLL: tumor biopsy immunohistochemistry diagnostic of SLL or blood/bone marrow immunophenotype similar to CLL without lymphocytosis and enlarged lymph nodes.
• Patient must have relapsed or refractory CLL/SLL following at least one purine analog-containing regimen (or after one non-purine analog containing regimen if there is a relative contraindication to purine-analog containing therapy) and not have traditional options available or decline these. Patients with prolymphocytic leukemia (PLL)-CLL or PLL transformation of CLL are eligible.
• Patients must meet IWCLL 2008 Guideline [13] criteria for active disease requiring treatment.

Each patient with NHL must meet all of the following inclusion criteria to be enrolled on the study:

• Patients with histologically confirmed B-cell NHL including marginal zone lymphoma, follicular lymphoma, or mantle cell lymphoma by WHO criteria.
• Patients must have relapsed or refractory disease after at least one prior therapy and not have traditional options available or decline these.

All patients must meet all of the following inclusion criteria to be enrolled on the study:

• Age ≥ 18 years
• Able to understand and sign a written informed consent document.
• Able to receive outpatient treatment and follow-up at the treating institution.
• ECOG performance status 0-1.
• Relapsed/refractory to at least one prior standard systemic treatment regimen, but no more than 4.
• Completed all prior therapies (immunosuppressive medications, antineoplastic therapy, vaccination, immunotherapy, chemotherapy, radiotherapy, major surgery, etc) >4 weeks prior to the first study dose of medication (alemtuzumab ≥ 6 months).
• If receiving corticosteroids, ≤ 20 mg/day prednisone or equivalent and unchanged
• Patients capable of reproduction and male patients who have partners capable of reproduction must agree to use an effective contraceptive method during the course of the study and for 2 months following the completion of their last treatment.
• Females of childbearing potential must have a negative serum β-Hcg pregnancy test result within 7 days of first study dose. Female patients who are surgically sterilized or who are > 45 years old and have not experienced menses for > 2 years may have β- Hcg pregnancy test waived.
• Required baseline laboratory data
• Platelet count ≥ 75,000/mm3
• Absolute neutrophil count (ANC) ≥ 1500/mm3
• AST/ALT ≤ 2.5 times upper limit of normal (ULN)
• Creatinine and total bilirubin ≤ 1.5 times ULN

Exclusion Criteria:

• Patients having received anti-CD20 therapy ≤ 4 weeks prior to the first study dose.
• Patients having received alemtuzumab (anti-CD52) therapy ≤ 6 months prior to the first study dose.
• Patients having undergone prior allogeneic stem cell transplantation within 6 months or having active graft versus host disease.
• Patients with active Richter's syndrome (>10% large B-cells in marrow).
• Patients that have been designated Class III or IV by the New York Heart Association Functional Classification.
• Patients with a history of myocardial infarction or stroke within the last 6 months
• Patients with transfusion-dependent anemia.
• Patients with known hypersensitivity to any excipient contained in the drug formulation.
• Patients with a history of documented human anti-globulin antibodies.
• Patients with active viral, bacterial or systemic fungal infection requiring treatment.
• Patients who are known to be HIV or hepatitis C positive.
• Patients with a history of prior secondary malignancy that requires active systemic therapy that will interfere with interpretation of efficacy or toxicity of IMMU-114, or limit survival to 2 years. These patients should be discussed with the sponsor prior to enrollment. Patients with basal or squamous skin carcinoma, cervical carcinoma in situ on biopsy, localized breast cancer requiring hormonal therapy or localized prostate cancer (Gleason score < 5) do not require discussion.
• Patients with active known CNS lymphoma. Patients with history of CNS leukemia now in remission are eligible for the trial.
• Patients who are pregnant or breast-feeding.
• Patients with major surgery or radiation therapy within 4 weeks prior to first study dose.
• Patients must have recovered all toxicities from prior therapy or radiation to grade 1 or less (excluding alopecia).
• Patients with substance abuse or other medical or psychiatric conditions that, in the opinion of the investigator, would confound study interpretation or affect the patient's ability to tolerate or complete the study.