A Phase I Dose Escalation Study of Immunotherapy With IMMU-114 in Patients With Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)
- 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  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  criteria for active disease requiring
Each patient with NHL must meet all of the following inclusion criteria to be enrolled on
- 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
- ECOG performance status <3
- Patients must be able to receive outpatient treatment and follow-up at the treating
- Patients must have completed all prior therapies (immunosuppressive medications,
antineoplastic therapy, vaccination, immunotherapy, chemotherapy, radiotherapy, etc)
> 4 weeks prior to the first study dose of medication. Palliative corticosteroids
for B-symptoms or corticosteroid therapy for treatment of autoimmune anemia and/or
thrombocytopenia at a dose of <20mg daily.
- Prior rituximab is permitted under the following conditions: Patients who are
rituximab-refractory defined as having less than a partial response to the previous
rituximab-containing regimen are eligible at any time. Patients who are
rituximab-sensitive, defines as having a complete response or partial response to the
last rituximab-containing regimen, are eligible at least 4 weeks after the last
infusion of rituximab.
- Patients who have relapsed after autologous stem cell transplant are eligible for the
study. Patients who have relapse after allogeneic stem cell transplant are eligible
for the study if the transplant occurred > 6 months prior to the study and the
patient has no active graft versus host disease.
- 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 3 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.
- All patients will undergo screening for Hepatitis B, C, and HIV infection. Patients
with a history of hepatitis B (surface antigen or core antibody positive) must take
lamivudine or equivalent drug during study therapy and for one year after completion
of all therapy. Patients with active hepatitis B or C infection are not eligible.
- Required baseline laboratory data (If the following laboratory studies are abnormal
secondary to the underlying malignancy as determined by the treating clinician, they
will not be used as inclusion or exclusion criteria.)
- Platelet count ≥50,000/mm3
- Absolute neutrophil count (ANC) ≥500/mm3 (ANC quantitation is inaccurate in the
presence of WBC >50,000/mm3 and therefore ANC in the setting of WBC >50,000/mm3 will
not be utilized as an inclusion or exclusion criterion.)
- Creatinine <2.0mg/dL
- AST/AST ≤2.5 times upper limit of normal (ULN)
- Total bilirubin ≤2.0 ULN
- Patients must possess the ability to understand and the willingness to sign a written
informed consent document.
- 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
- Patients with a history of myocardial infarction or stroke within the last 6 months.
- Patients with known hypersensitivity to any excipient contained in the drug
- Patients with a history of documented human anti-globulin antibodies.
- Patients with active viral, bacterial or systemic fungal infection requiring
- 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
- 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.